385:
362:
4947:
4902:
259:
4917:
284:
4872:
5037:
4842:
4977:
4887:
636:
5007:
391:
290:
5052:
4962:
40:
4932:
4857:
4992:
5022:
1541:. In addition and after costimulation from CD28 the optimal activation of expression of IL-2 and these pathways is induced. In summary therefore before a cell will make IL-2 in accordance with this pathway there have to be two reactions: TCR+HLA and protein complex on the one hand and CD28 costimulation on the other indeed mere IL-2 ligation to its receptor is too low affinity to enable pathway.
1689:
IL-15 and IL-15L, is not relying on "in trans" presentation by its receptor alpha chain. As a free cytokine, mammalian IL-2 that is secreted by activated T cells is important for a negative feedback loop by the stimulation of regulatory T cells, the latter being the cells with the highest constitutive IL-2Rα (aka CD25) expression. Besides this
1685:(IL-15L). This "IL-15Rα" receptor chain is similar to mammalian IL-15Rα, and in tetrapod evolution a duplication of its coding gene plus further diversification created mammalian IL-2Rα. Sequences, and structural analysis of grass carp IL-2, suggest that fish IL-2 binds IL-15Rα in a manner reminiscent of how mammalian IL-15 binds to IL-15Rα.
2352:
later entered the field with its own proprietary, mutated, recombinant protein and Cetus and Amgen were soon competing scientifically and in the courts; Cetus won the legal battles and forced Amgen out of the field. By 1990 Cetus had gotten aldesleukin approved in nine
European countries but in that
2037:
The commercial interest in local IL-2 therapy has been very low. Because only a very low dose IL-2 is used, treatment of a patient would cost about $ 500 commercial value of the patented IL-2. The commercial return on investment is too low to stimulate additional clinical studies for the registration
2046:
Usually, in the U.S., the higher dosage option is used, affected by cancer type, response to treatment and general patient health. Patients are typically treated for five consecutive days, three times a day, for fifteen minutes. The following approximately 10 days help the patient to recover between
1693:
loop, mammalian IL-2 also participates in a positive feedback loop because activated T cells enhance their own IL-2Rα expression. As in mammals, fish IL-2 also stimulates T cell proliferation and appears to preferentially stimulate regulatory T cells. Fish IL-2 induces the expression of cytokines of
1528:
Gene expression regulation for IL-2 can be on multiple levels or by different ways. One of the checkpoints (in other words one of the things which needs to be done before IL-2 is expressed) is that there must be signaling through a conjunction of a T Cell
Receptor (a TCR) and an HLA-peptide complex.
2321:
According to an immunology textbook: "IL-2 is particularly important historically, as it is the first type I cytokine that was cloned, the first type I cytokine for which a receptor component was cloned, and was the first short-chain type I cytokine whose receptor structure was solved. Many general
2242:
IL-2 does not follow the classical dose-response curve of chemotherapeutics. The immunological activity of high and low dose IL-2 show sharp contrast. This might be related to different distribution of IL-2 receptors (CD25, CD122, CD132) on different cell populations, resulting in different cells
1688:
Despite fish IL-2 and IL-15 sharing the same IL-15Rα chain, the stability of fish IL-2 is independent of it whereas IL-15 and especially IL-15L depend on binding to (co-presentation with) IL-15Rα for their stability and function. This suggests that, like in mammals, fish IL-2, in contrast to fish
1424:~ 10 M). Interaction of IL-2 and CD25 alone does not lead to signal transduction due to its short intracellular chain but has the ability (when bound to the β and γ subunit) to increase the IL-2R affinity 100-fold. Heterodimerization of the β and γ subunits of IL-2R is essential for signalling in
2380:
was developing a version called bioleukin, with a methionine added at is N-terminal and residue 125 replaced with alanine. Dozens of clinical trials had been conducted of recombinant or purified IL-2, alone, in combination with other drugs, or using cell therapies, in which cells were taken from
2074:
In local application, the systemic dose of IL-2 is too low to cause side effects, since the total dose is about 100 to 1000 fold lower. Clinical studies showed painful injections at the site of radiation as the most important side effect, reported by patients. In the case of irradiation of
2070:
Tumour blood vessels are more vulnerable than normal blood vessels to the actions of IL-2. When injected inside a tumor, i.e. local application, a process mechanistically similar to the vascular leakage syndrome, occurs in tumor tissue only. Disruption of the blood flow inside of the tumor
2197:). It is caused by lung endothelial cells expressing high-affinity IL-2R. These cells, as a result of IL-2 binding, causes increased vascular permeability. Thus, intravascular fluid extravasate into organs, predominantly lungs, which leads to life-threatening pulmonary or brain oedema.
2226:. This drug binds to IL-2 receptors and introduces the diphtheria toxin into cells that express those receptors, killing the cells. In some leukemias and lymphomas, malignant cells express the IL-2 receptor, so denileukin diftitox can kill them. In 1999 Ontak was approved by the
2322:
principles have been derived from studies of this cytokine including its being the first cytokine demonstrated to act in a growth factor–like fashion through specific high-affinity receptors, analogous to the growth factors being studied by endocrinologists and biochemists".
66:
1529:
As a result of that conjunction a signalling pathway (signalling a cell's protein making machinery to express or 'make' IL-2), a
PhosphoLipase-C (PLC) dependent pathway, is set up. PLC activates 3 major transcription factors and their pathways:
2894:
Bird S, Zou J, Kono T, Sakai M, Dijkstra JM, Secombes C (March 2005). "Characterisation and expression analysis of interleukin 2 (IL-2) and IL-21 homologues in the
Japanese pufferfish, Fugu rubripes, following their discovery by synteny".
2066:
In preclinical and early clinical studies, local application of IL-2 in the tumor has been shown to be clinically more effective in anticancer therapy than systemic IL-2 therapy, over a broad range of doses, without serious side effects.
1668:
in mounting and dampening immune responses. Through its role in the development of T cell immunologic memory, which depends upon the expansion of the number and function of antigen-selected T cell clones, it plays a key role in enduring
4946:
4242:
Hartemann A, Bensimon G, Payan CA, Jacqueminet S, Bourron O, Nicolas N, et al. (December 2013). "Low-dose interleukin 2 in patients with type 1 diabetes: a phase 1/2 randomised, double-blind, placebo-controlled trial".
2288:
half-life in circulation. Depending on the clone of IL-2 mAb, IL-2 ic can selectively stimulate either CD25 (IL-2/JES6-1 complexes), or CD122 cells (IL-2/S4B6). IL-2/S4B6 immune complexes have high stimulatory activity for
2257:
More recently low dose IL-2 has shown early success in modulating the immune system in disease like type 1 diabetes and vasculitis. There are also promising studies looking to use low dose IL-2 in ischaemic heart disease.
4901:
2337:-stimulated normal human lymphocytes. The key factor was isolated from cultured mouse cells in 1979 and from cultured human cells in 1980. The gene for human IL-2 was cloned in 1982 after an intense competition.
2050:
A lower dose regimen involves injection of IL-2 under the skin typically on an outpatient basis. It may alternatively be given on an inpatient basis over 1–3 days, similar to and often including the delivery of
2243:
that are activated by high and low dose IL-2. In general high doses are immune suppressive, while low doses can stimulate type 1 immunity. Low-dose IL-2 has been reported to reduce hepatitis C and B infection.
4916:
4871:
3816:"100% Complete response rate in patients with cutaneous metastatic melanoma treated with intralesional interleukin (IL)-2, imiquimod, and topical retinoid combination therapy: results of a case series"
4698:
1681:
IL-2 has been discovered in all classes of jawed vertebrates, including sharks, at a similar genomic location. In fish, IL-2 shares a single receptor alpha chain with its related cytokines IL-15 and
2203:
Intralesional IL-2 used to treat in-transit melanoma metastases is generally well tolerated. This is also the case for intralesional IL-2 in other forms of cancer, like nasopharyngeal carcinoma.
2385:
acquired Chiron in 2006 and licensed the US aldesleukin business to
Prometheus Laboratories in 2010 before global rights to Proleukin were subsequently acquired by Clinigen in 2018 and 2019.
6207:
3128:"Identification of a gene for an ancient cytokine, interleukin 15-like, in mammals; interleukins 2 and 15 co-evolved with this third family member, all sharing binding motifs for IL-15Rα"
2246:
IL-2 has been used in clinical trials for the treatment of chronic viral infections and as a booster (adjuvant) for vaccines. The use of large doses of IL-2 given every 6–8 weeks in
5036:
1809:
2087:, and the level of dosing usually determines the severity of the side effects. In the case of local IL-2 application, the therapeutic window spans several orders of magnitude.
1697:
As has been found in some studies on mammalian IL-2, data suggest that fish IL-2 can form homodimers and that this is an ancient property of the IL-2/15/15L-family cytokines.
1558:
has multiple family members, all of them are located in cytoplasm and signaling goes through calcineurin, NFAT is dephosphorylated and therefore translocated to the nucleus.
4170:
Tomova R, Pomakov J, Jacobs JJ, Adjarov D, Popova S, Altankova I, et al. (May–June 2006). "Changes in cytokine profile during local IL-2 therapy in cancer patients".
2018:
Neoleukin 2/15 is a computationally designed mimic of IL-2 that was designed to avoid common side effects. However, clinical trials into this candidate were discontinued.
3326:
Corripio-Miyar Y, Secombes CJ, Zou J (January 2012). "Long-term stimulation of trout head kidney cells with the cytokines MCSF, IL-2 and IL-6: gene expression dynamics".
5596:
3794:
398:
297:
3679:
4197:
Tomova R, Antonov K, Ivanova A, Jacobs JJ, Koten JW, Den Otter W, et al. (December 2009). "CLow-dose IL-2 therapy reduces HCV RNA and HBV DNA: case report".
2938:
Dijkstra JM (February 2021). "A method for making alignments of related protein sequences that share very little similarity; shark interleukin 2 as an example".
2691:"Different interleukin 2 receptor beta-chain tyrosines couple to at least two signaling pathways and synergistically mediate interleukin 2-induced proliferation"
6200:
1747:
3175:
Wang J, Wang W, Xu J, Jia Z, Liu Q, Zhu X, et al. (February 2021). "Structural insights into the co-evolution of IL-2 and its private receptor in fish".
2200:
Other drawbacks of IL-2 cancer immunotherapy are its short half-life in circulation and its ability to predominantly expand regulatory T cells at high doses.
4841:
4976:
4886:
1049:
2270:
agent due to significant drawbacks which are listed above. Some of the issues can be overcome using IL-2 ic. They are composed of IL-2 and some of its
1030:
220:
6193:
4554:
Whittington R, Faulds D (September 1993). "Interleukin-2. A review of its pharmacological properties and therapeutic use in patients with cancer".
2193:
or a variety of other possible complications. The most common adverse effect of high-dose IL-2 therapy is vascular leak syndrome (VLS; also termed
5672:
4381:
Chavez AR, Buchser W, Basse PH, Liang X, Appleman LJ, Maranchie JK, et al. (December 2009). "Pharmacologic administration of interleukin-2".
2603:
Wang X, Rickert M, Garcia KC (November 2005). "Structure of the quaternary complex of interleukin-2 with its alpha, beta, and gammac receptors".
3759:
7405:
6672:
6067:
4955:: Crystal Structure Of Human Interleukin-2 Y31C Covalently Modified At C31 With 3-Mercapto-1-(1,3,4,9-tetrahydro-B-carbolin-2-yl)-propan-1-one
3428:"Interleukin (IL)-2 Is a Key Regulator of T Helper 1 and T Helper 2 Cytokine Expression in Fish: Functional Characterization of Two Divergent
1622:, thus helping the body fight off infections. Together with other polarizing cytokines, IL-2 stimulates naive CD4 T cell differentiation into
7409:
7395:
7355:
4821:
4365:
3039:
Fang W, Shao JZ, Xiang LX (July 2007). "Molecular cloning and characterization of IL-15R alpha gene in rainbow trout (Oncorhynchus mykiss)".
2461:
1570:
is translocated to the nucleus after costimulation through CD28. NFkB is a heterodimer and there are two binding sites on the IL-2 promoter.
2443:
7470:
7424:
5006:
4617:
4060:"Correction for Krieg et al., Improved IL-2 immunotherapy by selective stimulation of IL-2 receptors on lymphocytes and endothelial cells"
4024:
Shaker MA, Younes HM (July 2009). "Interleukin-2: evaluation of routes of administration and current delivery systems in cancer therapy".
2357:(FDA) refused to approve Cetus' application to market IL-2. The failure led to the collapse of Cetus, and in 1991 the company was sold to
5051:
5092:
4961:
1249:
384:
7329:
4499:
6277:
5958:
4910:: Crystal Structure of Human Interleukin-2 Y31C Covalently Modified at C31 with (1H-Indol-3-yl)-(2-mercapto-ethoxyimino)-acetic acid
1256:
4635:
Dutcher JP (November 2002). "Current status of interleukin-2 therapy for metastatic renal cell carcinoma and metastatic melanoma".
4152:
3371:"Identification of Treg-like cells in Tetraodon: insight into the origin of regulatory T subsets during early vertebrate evolution"
361:
4699:"Novartis sells rights to Proleukin in the USA to Prometheus; gets license for vaccine from IIG; and pleads guilty over Trileptal"
4931:
4856:
4726:
7490:
5488:
4991:
2430:
2409:
1839:
1765:
1564:
is a dimer and is composed of c-Jun and c-Fos proteins. It cooperates with other transcription factors including NFkB and Oct.
3791:
2426:
283:
258:
63:
7290:
7269:
5265:
3084:"Functional characterization of the human interleukin-15 receptor alpha chain and close linkage of IL15RA and IL2RA genes"
2553:"IL-2 family cytokines: new insights into the complex roles of IL-2 as a broad regulator of T helper cell differentiation"
1607:
3687:
3223:"Competing feedback loops shape IL-2 signaling between helper and regulatory T lymphocytes in cellular microenvironments"
2405:
1452:
Instructions to express proteins in response to an IL-2 signal (called IL-2 transduction) can take place via 3 different
3283:
Boyman O, Sprent J (February 2012). "The role of interleukin-2 during homeostasis and activation of the immune system".
2354:
2227:
1993:
1935:
200:
3617:
1784:
6101:
5651:
5426:
4283:
for "Low Dose
Interleukin-2 in Patients With Stable Ischaemic Heart Disease and Acute Coronary Syndromes (LILACS)" at
4925:: Crystal Structure of Human Interleukin-2 K43C Covalently Modified at C43 with 2--N-(3-mercapto-propyl)-propionamide
2329:
proliferation. In the mid-1970s, it was discovered that T-cells could be selectively proliferated when normal human
1513:. with an "express other proteins" signal. The proteins expressed by means of the three pathways include bcl-6 (the
7485:
6134:
5936:
5646:
2058:
Intralesional IL-2 is commonly used to treat in-transit melanoma metastases and has a high complete response rate.
1606:, which suppress other T cells that are otherwise primed to attack normal healthy cells in the body. IL-2 enhances
1518:
1498:
1457:
397:
296:
5021:
4880:: Crystal Structure of Human IL-2 Complexed with (R)-N--1-oxoethyl]-4-(phenylethynyl)-L-phenylalanine methyl ester
2800:
Spolski R, Li P, Leonard WJ (2018). "Biology and regulation of IL-2: from molecular mechanisms to human therapy".
7480:
6055:
5740:
4814:
2802:
2231:
1538:
4680:
3661:
1664:
Its expression and secretion is tightly regulated and functions as part of both transient positive and negative
390:
289:
6090:
5517:
5493:
4598:
3967:
Jacobs JJ, Hordijk GJ, Jürgenliemk-Schulz IM, Terhaard CH, Koten JW, Battermann JJ, et al. (August 2005).
2654:
Gaffen SL, Liu KD (November 2004). "Overview of interleukin-2 function, production and clinical applications".
2493:
2047:
treatments. IL-2 is delivered intravenously on an inpatient basis to enable proper monitoring of side effects.
1989:
1599:
1468:
pathway. The signalling is commenced by IL-2 binding to its receptor, following which cytoplasmatic domains of
1094:
208:
3969:"Treatment of stage III-IV nasopharyngeal carcinomas by external beam irradiation and local low doses of IL-2"
2361:. Chiron continued the development of IL-2, which was finally approved by the FDA as Proleukin for metastatic
2075:
nasopharyngeal carcinoma the five-year disease-free survival increased from 8% to 63% by local IL-2 therapy
7248:
7208:
7187:
7131:
7099:
7058:
7016:
6970:
6889:
6863:
6807:
6766:
6740:
6714:
6368:
5085:
2194:
1795:
1075:
6823:
2250:
therapy, similar to its use in cancer therapy, was found to be ineffective in preventing progression to an
1365:. Put shortly the function of IL-2 is to stimulate the growth of helper, cytotoxic and regulatory T cells.
6683:
6663:
6642:
6561:
6500:
6444:
6398:
6322:
6227:
5418:
2344:
had created a proprietary recombinant version of IL-2 (Aldesleukin, later branded as
Proleukin), with the
1964:
1670:
1353:, and in discriminating between foreign ("non-self") and "self". IL-2 mediates its effects by binding to
7475:
2306:
1514:
1461:
6333:
3126:
Dijkstra JM, Takizawa F, Fischer U, Friedrich M, Soto-Lampe V, Lefèvre C, et al. (February 2014).
7445:
7228:
6216:
5944:
4807:
4390:
4309:
3714:
3335:
3234:
3048:
2702:
2612:
2298:
2005:
272:
6358:
3858:
Den Otter W, Jacobs JJ, Battermann JJ, Hordijk GJ, Krastev Z, Moiseeva EV, et al. (July 2008).
3221:
Busse D, de la Rosa M, Hobiger K, Thurley K, Flossdorf M, Scheffold A, et al. (February 2010).
1904:
187:
7495:
7219:
6777:
6572:
6348:
6242:
5786:
2290:
2271:
2215:
2139:
1869:
1700:
Homologues of IL-2 have not been reported for jawless fish (hagfish and lamprey) or invertebrates.
1654:
1595:
1453:
7089:
7084:
7069:
6981:
6960:
6409:
6343:
6302:
6246:
6219:
5953:
5910:
5825:
5668:
5532:
5078:
4579:
4414:
4335:
4284:
4134:
4006:
3946:
3598:
3408:
3308:
3200:
2963:
2920:
2827:
2636:
2524:
2358:
2340:
Commercial activity to bring an IL-2 drug to market was intense in the 1980s and 1990s. By 1983,
2334:
2310:
2084:
1603:
1583:
1414:
1410:
232:
6950:
6818:
6725:
6704:
6455:
6424:
6419:
6363:
6282:
1232:
1211:
1185:
1164:
6996:
6429:
6257:
6252:
3082:
Anderson DM, Kumaki S, Ahdieh M, Bertles J, Tometsko M, Loomis A, et al. (December 1995).
6602:
6587:
6551:
6521:
6267:
5817:
5436:
5302:
5045:: Crystal structure of the heterotrimeric interleukin-2 receptor in complex with interleukin-2
4779:
4767:
4644:
4571:
4495:
4463:
4406:
4361:
4327:
4260:
4206:
4179:
4126:
4081:
4041:
3998:
3938:
3889:
3837:
3740:
3639:
3590:
3555:
3504:
3463:
3400:
3351:
3300:
3262:
3192:
3157:
3105:
3064:
3021:
2955:
2912:
2876:
2819:
2779:
2730:
2671:
2628:
2582:
2516:
2369:
2341:
2302:
2182:
2114:
1997:
1854:
1737:
1690:
1579:
1441:
180:
56:
4434:"Purification of human interleukin 2 to apparent homogeneity and its molecular heterogeneity"
4225:"IL-2 Immunotherapy Fails to Benefit HIV-Infected Individuals Already Taking Antiretrovirals"
2325:
In the mid-1960s, studies reported "activities" in leukocyte-conditioned media that promoted
7440:
6129:
6050:
5918:
5607:
5441:
4757:
4749:
4563:
4531:
4453:
4445:
4398:
4317:
4252:
4118:
4089:
4071:
4033:
3988:
3980:
3928:
3920:
3909:"Local interleukin 2 therapy is most effective against cancer when injected intratumourally"
3879:
3871:
3827:
3730:
3722:
3701:
Silva DA, Yu S, Ulge UY, Spangler JB, Jude KM, Labão-Almeida C, et al. (January 2019).
3629:
3582:
3545:
3535:
3494:
3453:
3443:
3390:
3382:
3343:
3292:
3252:
3242:
3184:
3147:
3139:
3095:
3056:
3011:
3001:
2988:
Yamaguchi T, Chang CJ, Karger A, Keller M, Pfaff F, Wangkahart E, et al. (2020-10-29).
2947:
2904:
2866:
2858:
2811:
2769:
2761:
2720:
2710:
2663:
2620:
2572:
2564:
2508:
2294:
2223:
2163:
1878:
1658:
1639:
1611:
1522:
1465:
1335:
477:
408:
352:
307:
6916:
6912:
6908:
1944:
7232:
5656:
5342:
4730:
3798:
2377:
2362:
1985:
1491:
1343:
452:
228:
4394:
4313:
3993:
3968:
3933:
3908:
3718:
3395:
3370:
3339:
3238:
3052:
2706:
2616:
2372:
was also developing a proprietary, modified, recombinant IL-2 called teceleukin, with a
635:
7430:
7420:
7415:
7401:
7387:
7377:
7372:
7319:
7301:
7280:
7259:
7238:
7224:
7198:
7142:
7110:
7074:
7037:
7032:
7027:
6991:
6986:
6900:
6879:
6833:
6782:
6751:
6730:
6465:
6434:
6170:
6165:
6020:
6016:
5998:
5993:
5796:
5791:
5781:
5776:
5771:
5766:
5761:
5757:
5726:
5721:
5716:
5695:
5690:
5685:
5680:
5635:
5630:
5625:
5620:
5568:
5553:
5544:
5101:
4762:
4737:
4458:
4433:
4094:
4059:
3884:
3859:
3735:
3702:
3634:
3550:
3523:
3458:
3427:
3257:
3222:
3152:
3127:
3016:
2989:
2871:
2846:
2774:
2749:
2577:
2552:
2190:
1615:
1487:
1483:
1476:
1394:
1390:
4256:
4224:
964:
959:
954:
949:
944:
939:
934:
929:
924:
919:
914:
909:
904:
899:
894:
889:
884:
879:
874:
869:
864:
859:
854:
849:
844:
839:
834:
829:
824:
819:
814:
809:
804:
799:
794:
789:
784:
779:
774:
769:
764:
759:
754:
738:
733:
728:
712:
707:
702:
697:
692:
687:
682:
677:
39:
7464:
7172:
6828:
6694:
6653:
6577:
6511:
6460:
6414:
6238:
6160:
6155:
6150:
6096:
6045:
5711:
5615:
5591:
5586:
5563:
5558:
5549:
5322:
4788:
4723:
4583:
4567:
4488:
4402:
4138:
4122:
3586:
3204:
2967:
2750:"Interleukin-2 at the crossroads of effector responses, tolerance, and immunotherapy"
2725:
2690:
2267:
2027:
1398:
1386:
1382:
1378:
1362:
1358:
1354:
1328:
1324:
664:
4662:
4536:
4339:
4010:
3950:
3814:
Shi VY, Tran K, Patel F, Leventhal J, Konia T, Fung MA, et al. (October 2015).
3602:
3412:
3312:
2831:
2640:
7346:
7167:
6853:
6848:
6843:
6592:
6531:
6490:
5641:
5473:
4516:
4418:
2924:
2847:"Interleukin-2 receptor signaling: at the interface between tolerance and immunity"
2528:
2052:
1822:
1817:
1757:
1506:
1480:
1374:
470:
249:
6185:
4279:
3483:"Carbohydrate recognition site of interleukin-2 in relation to cell proliferation"
1428:. IL-2 can signalize either via intermediate-affinity dimeric CD122/CD132 IL-2R (K
212:
4298:"Selective stimulation of T cell subsets with antibody-cytokine immune complexes"
2862:
2765:
2008:) in large intermittent doses and has been extensively used in continuous doses.
236:
7177:
7157:
7120:
6955:
6945:
6797:
6792:
6627:
6597:
6536:
6378:
6338:
6297:
6292:
6062:
6008:
5749:
5508:
5431:
4360:(6th ed.). Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins.
2990:"Ancient Cytokine Interleukin 15-Like (IL-15L) Induces a Type 2 Immune Response"
2466:
National Center for
Biotechnology Information, U.S. National Library of Medicine
2448:
National Center for
Biotechnology Information, U.S. National Library of Medicine
2330:
2149:
2106:
2031:
1981:
1802:
1316:
4432:
Welte K, Wang CY, Mertelsmann R, Venuta S, Feldman SP, Moore MA (August 1982).
3832:
3815:
3426:
Wang T, Hu Y, Wangkahart E, Liu F, Wang A, Zahran E, et al. (2018-07-26).
3227:
Proceedings of the
National Academy of Sciences of the United States of America
2951:
2695:
Proceedings of the National Academy of Sciences of the United States of America
2667:
553:
7162:
7152:
7047:
6940:
6935:
6756:
6617:
6607:
6541:
6475:
6388:
6383:
6312:
6115:
5808:
5498:
5458:
3984:
3924:
3875:
3726:
3386:
3347:
3188:
3143:
3060:
3006:
2908:
2815:
2568:
2373:
2326:
2154:
2110:
1712:
are poorly understood, some evidence indicates that IL-2 is involved in itchy
1682:
1548:
is expressed. It helps the activation. Oct1 is expressed in T-lymphocytes and
1357:, which are expressed by lymphocytes. The major sources of IL-2 are activated
1339:
369:
266:
216:
4753:
4085:
3448:
3100:
3083:
2512:
6632:
6622:
6612:
6485:
5120:
5070:
4322:
4297:
4076:
3247:
2624:
2218:(trade name Ontak), which is a recombinant fusion protein of the human IL-2
2174:
2170:
2158:
1751:
1725:
1713:
1350:
1347:
994:
613:
491:
436:
423:
335:
322:
224:
4771:
4648:
4410:
4331:
4264:
4210:
4183:
4130:
4045:
4002:
3942:
3893:
3841:
3744:
3643:
3594:
3559:
3508:
3499:
3482:
3467:
3404:
3355:
3304:
3266:
3196:
3161:
3068:
3025:
2959:
2916:
2880:
2823:
2783:
2715:
2675:
2632:
2586:
2520:
4575:
4467:
4449:
3760:"Neoleukin Drops de Novo Protein Therapeutic, Slashes Workforce - Updated"
3109:
2734:
1296:
1291:
6272:
6110:
5105:
3540:
2382:
2285:
2251:
2144:
2135:
2124:
2102:
2001:
1915:
1779:
1709:
1665:
1631:
1623:
1494:
1437:
1320:
1280:
1139:
1120:
17:
4157:
Package Insert to Include a Description of Ophthalmologic Adverse Events
1924:
855:
protein kinase C-activating G protein-coupled receptor signaling pathway
7391:
6874:
4793:
4783:
3573:
Noble S, Goa KL (May 1997). "Aldesleukin (recombinant interleukin-2)".
2345:
2276:
2178:
1889:
1619:
1587:
1331:
1106:
1061:
4037:
157:
153:
149:
145:
141:
137:
133:
129:
125:
121:
117:
113:
109:
105:
101:
97:
93:
89:
85:
7006:
5988:
5885:
5880:
5875:
5870:
5865:
5860:
5578:
5383:
5367:
5362:
5357:
5352:
5347:
5337:
5332:
4494:(Paperback ed.). Chicago, IL, USA: University of Chicago Press.
2219:
2120:
2012:
1955:
1591:
1425:
1264:
1016:
3296:
2169:
More serious and dangerous side effects sometimes are seen, such as
1420:
The IL-2 receptor (IL-2R) α subunit binds IL-2 with low affinity (K
7313:
7309:
7305:
6924:
6920:
6904:
6024:
5983:
5978:
5973:
5968:
5963:
5900:
5890:
5855:
5850:
5845:
5840:
5835:
5830:
5483:
5478:
5468:
5453:
5448:
5327:
5317:
5312:
5307:
5297:
5292:
5286:
5270:
5260:
5255:
5250:
5245:
5240:
5235:
5230:
5225:
5219:
5214:
5209:
5204:
5199:
5194:
5189:
5184:
4850:: THE SOLUTION STRUCTURE OF THE F42A MUTANT OF HUMAN INTERLEUKIN 2
4296:
Boyman O, Kovar M, Rubinstein MP, Surh CD, Sprent J (March 2006).
2349:
2348:
removed from its N-terminal and residue 125 replaced with serine.
2211:
2186:
2098:
1545:
1502:
1473:
1469:
1406:
1402:
1373:
IL-2 is a member of a cytokine family, each member of which has a
4985:: Structure of a 60 nM Small Molecule Bound to a Hot Spot on IL-2
4895:: Crystal Structure of Human Interleukin-2 Complexed with SP-1985
3703:"De novo design of potent and selective mimics of IL-2 and IL-15"
1984:
is a form of recombinant interleukin-2. It is manufactured using
979:
975:
5948:
5895:
5463:
5404:
5399:
5179:
5174:
5169:
5164:
5158:
5152:
5146:
5140:
5135:
2130:
2000:
and in several European countries for the treatment of cancers (
1578:
IL-2 has essential roles in key functions of the immune system,
1549:
1534:
1530:
1342:) that are responsible for immunity. IL-2 is part of the body's
204:
6189:
5074:
4803:
2368:
By 1993 aldesleukin was the only approved version of IL-2, but
1848:
1774:
940:
positive regulation of tyrosine phosphorylation of STAT protein
644:
7381:
4799:
2689:
Friedmann MC, Migone TS, Russell SM, Leonard WJ (March 1996).
2301:. On the other hand, IL-2/JES6-1 highly selectively stimulate
2247:
2094:
1510:
1436:~ 10 M). Dimeric IL-2R is expressed by memory CD8 T cells and
3481:
Fukushima K, Hara-Kuge S, Ideo H, Yamashita K (August 2001).
1444:
and activated T cells express high levels of trimeric IL-2R.
4778:
Overview of all the structural information available in the
4718:
4109:
Figgitt DP, Lamb HM, Goa KL (2000). "Denileukin diftitox".
1432:~ 10 M) or high-affinity trimeric CD25/CD122/CD132 IL-2R (K
4738:"IL-2: the first effective immunotherapy for human cancer"
3786:
3784:
3782:
3780:
2254:
diagnosis in two large clinical trials published in 2009.
890:
extrinsic apoptotic signaling pathway in absence of ligand
795:
positive regulation of cytosolic calcium ion concentration
4231:. National Institutes of Health (NIH). February 10, 2009.
2492:
Arenas-Ramirez N, Woytschak J, Boyman O (December 2015).
1610:. IL-2 also promotes the differentiation of T cells into
920:
positive regulation of transcription by RNA polymerase II
3369:
Wen Y, Fang W, Xiang LX, Pan RL, Shao JZ (August 2011).
2333:
cells were cultured in conditioned medium obtained from
900:
positive regulation of isotype switching to IgG isotypes
800:
positive regulation of regulatory T cell differentiation
460:
2034:
of different dosages is often a point of disagreement.
930:
negative regulation of T-helper 17 cell differentiation
3669:
This source mentions approval in 9 European countries.
1992:
and branded as Proleukin. It has been approved by the
1401:, a complex consisting of three chains, termed alpha (
3809:
3807:
2297:
and they could thus replace the conventional IL-2 in
925:
positive regulation of activated T cell proliferation
625:
5015:: structure of interleukin-2 with its alpha receptor
1417:). The gamma chain is shared by all family members.
885:
positive regulation of cell population proliferation
7365:
7345:
7338:
7289:
7268:
7247:
7207:
7186:
7130:
7098:
7057:
7015:
6969:
6888:
6862:
6806:
6765:
6739:
6713:
6682:
6662:
6641:
6560:
6499:
6443:
6397:
6321:
6226:
6080:
6038:
6007:
5935:
5909:
5816:
5807:
5748:
5739:
5704:
5667:
5605:
5577:
5531:
5516:
5507:
5417:
5392:
5376:
5279:
5128:
5119:
5112:
4549:
4547:
2274:(mAb) and can potentiate biologic activity of IL-2
1954:
1934:
1914:
1888:
1868:
1863:
1838:
1833:
1808:
1794:
1764:
1746:
1736:
1731:
1225:
1204:
1178:
1157:
5060:: UNRAVELING THE STRUCTURE OF INTERLEUKIN-2: REPLY
4487:
2422:
2420:
2418:
2401:
2399:
2397:
1638:lymphocytes while it impedes differentiation into
825:positive regulation of dendritic spine development
810:positive regulation of interferon-gamma production
4970:: Low Micromolar Small Molecule Inhibitor of IL-2
3907:Jacobs JJ, Sparendam D, Den Otter W (July 2005).
1653:IL-2 increases the cell killing activity of both
1618:when the initial T cell is also stimulated by an
407:
306:
2494:"Interleukin-2: Biology, Design and Application"
2030:and across the world are used. The efficacy and
1903:
935:leukocyte activation involved in immune response
905:positive regulation of interleukin-17 production
4064:Proceedings of the National Academy of Sciences
3962:
3960:
3853:
3851:
3655:
3653:
3618:"Treatment of metastatic melanoma: an overview"
2795:
2793:
2381:patients, activated with IL-2, then reinfused.
2266:IL-2 cannot accomplish its role as a promising
1877:
945:regulation of regulatory T cell differentiation
895:negative regulation of B cell apoptotic process
830:negative regulation of lymphocyte proliferation
3820:Journal of the American Academy of Dermatology
2427:GRCm38: Ensembl release 89: ENSMUSG00000027720
840:regulation of T cell homeostatic proliferation
770:positive regulation of protein phosphorylation
760:negative regulation of protein phosphorylation
6201:
5086:
4815:
4153:"Changes in the Ontak (denileukin diftitiox)"
3616:Bhatia S, Tykodi SS, Thompson JA (May 2009).
2262:IL-2/anti-IL-2 mAb immune complexes (IL-2 ic)
1694:both type 1 (Th1) and type 2 (Th2) immunity.
755:positive regulation of T cell differentiation
8:
4524:Brazilian Journal of Pharmaceutical Sciences
4517:"Drugs obtained by biotechnology processing"
4481:
4479:
4477:
1783:
1724:
915:negative regulation of inflammatory response
775:positive regulation of inflammatory response
765:G protein-coupled receptor signaling pathway
4681:"Chiron shareholders approve Novartis deal"
2748:Liao W, Lin JX, Leonard WJ (January 2013).
2551:Liao W, Lin JX, Leonard WJ (October 2011).
2546:
2544:
2542:
2540:
2538:
2406:GRCh38: Ensembl release 89: ENSG00000109471
2015:at residue 125, sold by Shenzhen Neptunus.
875:positive regulation of T cell proliferation
865:positive regulation of B cell proliferation
7342:
6208:
6194:
6186:
5813:
5745:
5528:
5513:
5125:
5116:
5093:
5079:
5071:
4940:: Crystal Structure of Human Interleukin-2
4865:: Crystal Structure of Human Interleukin-2
4822:
4808:
4800:
4383:Annals of the New York Academy of Sciences
4351:
4349:
990:
660:
448:
347:
244:
74:
4761:
4535:
4457:
4321:
4093:
4075:
3992:
3932:
3883:
3831:
3734:
3633:
3549:
3539:
3498:
3457:
3447:
3394:
3256:
3246:
3151:
3099:
3015:
3005:
2870:
2773:
2724:
2714:
2576:
2305:and they could be potentially useful for
1943:
950:regulation of signaling receptor activity
7373:Interleukin 14 (taxilin alpha, HMW-BCGF)
5000:: Structure of SP4160 Bound to IL-2 V69A
4618:"Cetus: A Collision Course With Failure"
4245:The Lancet. Diabetes & Endocrinology
4111:American Journal of Clinical Dermatology
3860:"Local therapy of cancer with free IL-2"
3177:Developmental and Comparative Immunology
2280:. The main mechanism of this phenomenon
1497:on CD122. This phosphorylation recruits
960:interleukin-2-mediated signaling pathway
870:positive regulation of tissue remodeling
820:negative regulation of apoptotic process
785:negative regulation of heart contraction
4837:
2393:
2011:Interking is a recombinant IL-2 with a
1923:
191:, IL-2, TCGF, lymphokine, interleukin 2
6671:See CXCR1 (IL-8Rα) and CXCR2 (IL-8Rβ)
1723:
1586:, primarily via its direct effects on
1448:IL-2 signaling pathways and regulation
965:positive regulation of kinase activity
29:
3278:
3276:
3216:
3214:
3121:
3119:
2983:
2981:
2979:
2977:
1963:
1756:
412:
373:
368:
311:
270:
265:
7:
4490:Making PCR: A story of biotechnology
4438:The Journal of Experimental Medicine
3524:"Mediators of pruritus in psoriasis"
3375:Cellular and Molecular Life Sciences
2598:
2596:
2487:
2485:
2483:
2481:
2479:
2477:
2475:
1894:
1821:
1608:activation-induced cell death (AICD)
1594:, where T cells mature, it prevents
1505:, which dimerize and migrate to the
3487:The Journal of Biological Chemistry
3088:The Journal of Biological Chemistry
2071:effectively destroys tumor tissue.
2026:Various dosages of IL-2 across the
955:cytokine-mediated signaling pathway
4026:Journal of Pharmaceutical Sciences
2845:Malek TR, Castro I (August 2010).
2284:is due to the prolongation of the
1552:is induced after cell activation.
1521:pathway) and certain cyclins (the
1479:. This leads to the activation of
1222:
1201:
1175:
1154:
1130:
1111:
1085:
1066:
1040:
1021:
850:positive regulation of cell growth
734:intracellular anatomical structure
703:kappa-type opioid receptor binding
630:
548:
486:
465:
25:
3662:"Cetus Drug Is Blocked By F.D.A."
3522:Reich A, Szepietowski JC (2007).
2228:U.S. Food and Drug Administration
1602:of certain immature T cells into
1517:pathway), CD25 & prdm-1 (the
1334:that regulates the activities of
27:Mammalian protein found in humans
5050:
5035:
5020:
5005:
4990:
4975:
4960:
4945:
4930:
4915:
4900:
4885:
4870:
4855:
4840:
4568:10.2165/00003495-199346030-00009
4403:10.1111/j.1749-6632.2009.05160.x
4123:10.2165/00128071-200001010-00008
3913:Cancer Immunology, Immunotherapy
3864:Cancer Immunology, Immunotherapy
3587:10.2165/00063030-199707050-00007
1988:technology and is marketed as a
634:
396:
389:
383:
360:
295:
288:
282:
257:
38:
7199:Interleukin 27 (interleukin 30)
4537:10.1590/s1984-82502011000200002
3328:Fish & Shellfish Immunology
3041:Fish & Shellfish Immunology
4616:Lehrman S (January 20, 1992).
3686:. 3 March 2014. Archived from
3680:"Shenzhen Neptunus Interlng-H"
2038:of intratumoral IL-2 therapy.
815:natural killer cell activation
683:interleukin-2 receptor binding
645:More reference expression data
614:More reference expression data
1:
4599:"2 Biotech Pioneers To Merge"
4515:Almeida H (April–June 2011).
4257:10.1016/S2213-8587(13)70113-X
3758:Scott R (November 15, 2022).
2557:Current Opinion in Immunology
1327:. It is a 15.5–16
381:
280:
2863:10.1016/j.immuni.2010.08.004
2766:10.1016/j.immuni.2013.01.004
2376:added at is N-terminal, and
2355:Food and Drug Administration
1994:Food and Drug Administration
7471:Genes on human chromosome 4
6549:Antisense oligonucleotides:
5030:: cytokine receptor complex
4597:Pollack A (July 23, 1991).
4117:(1): 67–72, discussion 73.
3801:. Date accessed: 07 Nov 10.
3792:Interleukin-2 (Aldesleukin)
3660:Pollack A (July 31, 1990).
2083:Systemic IL-2 has a narrow
1397:. IL-2 signals through the
1377:; the family also includes
7512:
4736:Rosenberg SA (June 2014).
3833:10.1016/j.jaad.2015.06.060
3285:Nature Reviews. Immunology
2952:10.1007/s00251-020-01191-5
2668:10.1016/j.cyto.2004.06.010
2090:Some common side effects:
1499:STAT transcription factors
1323:signaling molecule in the
6056:Colony-stimulating factor
4835:
3985:10.1007/s00262-004-0627-4
3973:Cancer Immunol Immunother
3925:10.1007/s00262-004-0627-4
3876:10.1007/s00262-008-0455-z
3790:American Cancer Society.
3727:10.1038/s41586-018-0830-7
3528:Mediators of Inflammation
3387:10.1007/s00018-010-0574-5
3348:10.1016/j.fsi.2011.10.016
3189:10.1016/j.dci.2020.103895
3144:10.1007/s00251-013-0747-0
3061:10.1016/j.fsi.2006.09.011
3007:10.3389/fimmu.2020.549319
2909:10.1007/s00251-004-0741-7
2816:10.1038/s41577-018-0046-y
2803:Nature Reviews Immunology
2569:10.1016/j.coi.2011.08.003
2462:"Mouse PubMed Reference:"
2444:"Human PubMed Reference:"
2232:cutaneous T cell lymphoma
2207:Pharmaceutical derivative
1295:
1290:
1286:
1279:
1263:
1250:Chr 4: 122.45 – 122.46 Mb
1244:
1229:
1208:
1197:
1182:
1161:
1150:
1137:
1133:
1118:
1114:
1105:
1092:
1088:
1073:
1069:
1060:
1047:
1043:
1028:
1024:
1015:
1000:
993:
989:
973:
693:kinase activator activity
688:glycosphingolipid binding
663:
659:
642:
633:
624:
611:
560:
551:
498:
489:
459:
451:
447:
430:
417:
380:
359:
350:
346:
329:
316:
279:
256:
247:
243:
198:
195:
185:
178:
173:
82:
77:
60:
55:
50:
46:
37:
32:
6091:proinflammatory cytokine
4754:10.4049/jimmunol.1490019
3449:10.3389/fimmu.2018.01683
3101:10.1074/jbc.270.50.29862
2513:10.1016/j.it.2015.10.003
1977:Pharmaceutical analogues
780:adaptive immune response
7239:Interleukin-29 (IFN-λ1)
6384:Daclizumab (dacliximab)
6369:Tucotuzumab celmoleukin
4792:(Interleukin-2) at the
4323:10.1126/science.1122927
4077:10.1073/pnas.1119897109
3436:Frontiers in Immunology
3248:10.1073/pnas.0812851107
2994:Frontiers in Immunology
2625:10.1126/science.1117893
2230:(FDA) for treatment of
2195:capillary leak syndrome
1375:four alpha helix bundle
1257:Chr 3: 37.17 – 37.18 Mb
7491:Immunomodulating drugs
7220:Interferon λ4 (IFN-λ4)
6313:Rilonacept (IL-1 Trap)
5222:/PARC/DCCK1/AMAC1/MIP4
4724:IL-2 Signaling Pathway
4622:The Scientist Magazine
4358:Fundamental immunology
4277:Clinical trial number
4070:(1): 345. 2011-12-28.
3684:Bloomberg BusinessWeek
3500:10.1074/jbc.M102789200
3432:Paralogs in Salmonids"
2716:10.1073/pnas.93.5.2077
2214:markets a drug called
1671:cell-mediated immunity
845:T cell differentiation
698:growth factor activity
7143:Interleukin 23 (SGRF)
6824:Cintredekin besudotox
6752:Interleukin 11 (AGIF)
6731:Interleukin 10 (CSIF)
4742:Journal of Immunology
4663:"D02749 (Teceleukin)"
4643:(11 Suppl 13): 4–10.
4450:10.1084/jem.156.2.454
3690:on February 27, 2011.
790:immune system process
6217:Interleukin receptor
4159:. FDA. May 11, 2009.
2501:Trends in Immunology
2309:and in treatment of
2299:cancer immunotherapy
2238:Preclinical research
1708:While the causes of
1655:natural killer cells
1464:pathway and (3) the
1456:; they are: (1) the
729:extracellular region
708:carbohydrate binding
375:Chromosome 3 (mouse)
273:Chromosome 4 (human)
78:List of PDB id codes
51:Available structures
6349:Denileukin diftitox
5787:Interferon type III
4705:. January 27, 2010.
4395:2009NYASA1182...14C
4314:2006Sci...311.1924B
4199:Anticancer Research
4172:Anticancer Research
3719:2019Natur.565..186S
3493:(33): 31202–31208.
3340:2012FSI....32...35C
3239:2010PNAS..107.3058B
3094:(50): 29862–29869.
3053:2007FSI....23..119F
2707:1996PNAS...93.2077F
2617:2005Sci...310.1159W
2311:autoimmune diseases
2272:monoclonal antibody
2216:denileukin diftitox
2140:shortness of breath
2129:dry, itchy skin or
1990:protein therapeutic
1728:
1596:autoimmune diseases
1509:where they bind to
1490:which subsequently
1338:(leukocytes, often
910:response to ethanol
805:cell-cell signaling
739:extracellular space
572:ganglionic eminence
6921:E (interleukin 25)
4729:2020-01-11 at the
4486:Rabinow P (1997).
4285:ClinicalTrials.gov
3797:2015-02-12 at the
3541:10.1155/2007/64727
2359:Chiron Corporation
2335:phytohemagglutinin
2303:regulatory T cells
2183:allergic reactions
2173:problems, serious
2150:low blood pressure
2085:therapeutic window
2002:malignant melanoma
1604:regulatory T cells
1454:signaling pathways
1442:regulatory T cells
1095:ENSMUSG00000027720
748:Biological process
722:Cellular component
671:Molecular function
414:3 B|3 18.3 cM
7486:Cancer treatments
7458:
7457:
7454:
7453:
7423:(signals through
7404:(signals through
7390:(signals through
7380:(signals through
7004:Binding proteins:
6334:Adargileukin alfa
6183:
6182:
6076:
6075:
6034:
6033:
5931:
5930:
5927:
5926:
5735:
5734:
5413:
5412:
5068:
5067:
4719:Proleukin website
4367:978-0-7817-6519-0
4038:10.1002/jps.21596
3713:(7738): 186–191.
3381:(15): 2615–2626.
2611:(5751): 1159–63.
2342:Cetus Corporation
2268:immunotherapeutic
2062:Local application
2006:renal cell cancer
1998:black box warning
1974:
1973:
1852:
1777:
1691:negative feedback
1659:cytotoxic T cells
1598:by promoting the
1544:At the same time
1460:pathway, (2) the
1336:white blood cells
1306:
1305:
1302:
1301:
1275:
1274:
1240:
1239:
1219:
1218:
1193:
1192:
1172:
1171:
1146:
1145:
1127:
1126:
1101:
1100:
1082:
1081:
1056:
1055:
1037:
1036:
985:
984:
678:cytokine activity
655:
654:
651:
650:
620:
619:
607:
606:
545:
544:
443:
442:
342:
341:
169:
168:
165:
164:
61:Ortholog search:
16:(Redirected from
7503:
7481:Immunostimulants
7446:Efineptakin alfa
7441:Efavaleukin alfa
7343:
6310:Decoy receptors:
6210:
6203:
6196:
6187:
5814:
5746:
5529:
5514:
5126:
5117:
5095:
5088:
5081:
5072:
5054:
5039:
5024:
5009:
4994:
4979:
4964:
4949:
4934:
4919:
4904:
4889:
4874:
4859:
4844:
4824:
4817:
4810:
4801:
4775:
4765:
4707:
4706:
4695:
4689:
4688:
4685:SWI swissinfo.ch
4677:
4671:
4670:
4659:
4653:
4652:
4632:
4626:
4625:
4613:
4607:
4606:
4594:
4588:
4587:
4551:
4542:
4541:
4539:
4521:
4512:
4506:
4505:
4493:
4483:
4472:
4471:
4461:
4429:
4423:
4422:
4378:
4372:
4371:
4356:Paul WE (2008).
4353:
4344:
4343:
4325:
4308:(5769): 1924–7.
4293:
4287:
4275:
4269:
4268:
4239:
4233:
4232:
4221:
4215:
4214:
4194:
4188:
4187:
4167:
4161:
4160:
4149:
4143:
4142:
4106:
4100:
4099:
4097:
4079:
4056:
4050:
4049:
4021:
4015:
4014:
3996:
3964:
3955:
3954:
3936:
3904:
3898:
3897:
3887:
3855:
3846:
3845:
3835:
3811:
3802:
3788:
3775:
3774:
3772:
3770:
3755:
3749:
3748:
3738:
3698:
3692:
3691:
3676:
3670:
3668:
3657:
3648:
3647:
3637:
3613:
3607:
3606:
3570:
3564:
3563:
3553:
3543:
3519:
3513:
3512:
3502:
3478:
3472:
3471:
3461:
3451:
3423:
3417:
3416:
3398:
3366:
3360:
3359:
3323:
3317:
3316:
3280:
3271:
3270:
3260:
3250:
3233:(7): 3058–3063.
3218:
3209:
3208:
3172:
3166:
3165:
3155:
3123:
3114:
3113:
3103:
3079:
3073:
3072:
3036:
3030:
3029:
3019:
3009:
2985:
2972:
2971:
2935:
2929:
2928:
2891:
2885:
2884:
2874:
2842:
2836:
2835:
2797:
2788:
2787:
2777:
2745:
2739:
2738:
2728:
2718:
2686:
2680:
2679:
2651:
2645:
2644:
2600:
2591:
2590:
2580:
2548:
2533:
2532:
2498:
2489:
2470:
2469:
2458:
2452:
2451:
2440:
2434:
2424:
2413:
2403:
2307:transplantations
2224:diphtheria toxin
2164:loss of appetite
2097:-like symptoms (
1967:
1947:
1927:
1907:
1897:
1896:
1881:
1850:
1847:
1825:
1787:
1776:
1773:
1760:
1729:
1727:
1612:effector T cells
1501:, predominantly
1344:natural response
1288:
1287:
1259:
1252:
1235:
1223:
1214:
1202:
1198:RefSeq (protein)
1188:
1176:
1167:
1155:
1131:
1112:
1086:
1067:
1041:
1022:
991:
661:
647:
638:
631:
616:
600:ventricular zone
556:
554:Top expressed in
549:
494:
492:Top expressed in
487:
466:
449:
439:
426:
415:
400:
393:
387:
376:
364:
348:
338:
325:
314:
299:
292:
286:
275:
261:
245:
239:
190:
183:
160:
75:
69:
48:
47:
42:
30:
21:
7511:
7510:
7506:
7505:
7504:
7502:
7501:
7500:
7461:
7460:
7459:
7450:
7361:
7334:
7285:
7264:
7243:
7203:
7182:
7126:
7123:(against IL-22)
7094:
7053:
7050:(against IL-20)
7011:
6965:
6884:
6858:
6802:
6761:
6735:
6709:
6678:
6658:
6637:
6556:
6495:
6439:
6393:
6317:
6222:
6214:
6184:
6179:
6145:
6124:
6082:
6072:
6030:
6003:
5923:
5905:
5803:
5731:
5700:
5663:
5601:
5573:
5524:
5522:
5520:
5503:
5409:
5388:
5372:
5275:
5108:
5099:
5069:
5064:
5061:
5055:
5046:
5040:
5031:
5025:
5016:
5010:
5001:
4995:
4986:
4980:
4971:
4965:
4956:
4950:
4941:
4935:
4926:
4920:
4911:
4905:
4896:
4890:
4881:
4875:
4866:
4860:
4851:
4845:
4831:
4828:
4735:
4731:Wayback Machine
4715:
4710:
4697:
4696:
4692:
4687:. Apr 19, 2006.
4679:
4678:
4674:
4661:
4660:
4656:
4634:
4633:
4629:
4615:
4614:
4610:
4596:
4595:
4591:
4553:
4552:
4545:
4519:
4514:
4513:
4509:
4502:
4485:
4484:
4475:
4431:
4430:
4426:
4380:
4379:
4375:
4368:
4355:
4354:
4347:
4295:
4294:
4290:
4276:
4272:
4241:
4240:
4236:
4223:
4222:
4218:
4196:
4195:
4191:
4178:(3A): 2037–47.
4169:
4168:
4164:
4151:
4150:
4146:
4108:
4107:
4103:
4058:
4057:
4053:
4023:
4022:
4018:
3966:
3965:
3958:
3906:
3905:
3901:
3857:
3856:
3849:
3813:
3812:
3805:
3799:Wayback Machine
3789:
3778:
3768:
3766:
3757:
3756:
3752:
3700:
3699:
3695:
3678:
3677:
3673:
3659:
3658:
3651:
3615:
3614:
3610:
3572:
3571:
3567:
3521:
3520:
3516:
3480:
3479:
3475:
3425:
3424:
3420:
3368:
3367:
3363:
3325:
3324:
3320:
3297:10.1038/nri3156
3282:
3281:
3274:
3220:
3219:
3212:
3174:
3173:
3169:
3125:
3124:
3117:
3081:
3080:
3076:
3038:
3037:
3033:
2987:
2986:
2975:
2937:
2936:
2932:
2903:(12): 909–923.
2893:
2892:
2888:
2844:
2843:
2839:
2810:(10): 648–659.
2799:
2798:
2791:
2747:
2746:
2742:
2688:
2687:
2683:
2653:
2652:
2648:
2602:
2601:
2594:
2550:
2549:
2536:
2507:(12): 763–777.
2496:
2491:
2490:
2473:
2460:
2459:
2455:
2442:
2441:
2437:
2425:
2416:
2404:
2395:
2391:
2363:renal carcinoma
2353:year, the U.S.
2319:
2264:
2240:
2209:
2081:
2064:
2044:
2024:
1986:recombinant DNA
1979:
1970:
1950:
1930:
1910:
1893:
1884:
1859:
1829:
1797:
1790:
1722:
1706:
1704:Role in disease
1679:
1649:
1646:and folicular T
1643:
1635:
1627:
1600:differentiation
1576:
1450:
1435:
1431:
1423:
1371:
1297:View/Edit Mouse
1292:View/Edit Human
1255:
1248:
1245:Location (UCSC)
1231:
1210:
1184:
1163:
1076:ENSG00000109471
969:
880:immune response
743:
717:
713:protein binding
643:
612:
603:
598:
594:
590:
586:
582:
578:
574:
570:
566:
552:
541:
536:
532:
528:
524:
520:
516:
512:
508:
504:
490:
434:
421:
413:
403:
402:
401:
394:
374:
351:Gene location (
333:
320:
312:
302:
301:
300:
293:
271:
248:Gene location (
237:IL2 - orthologs
199:
186:
179:
84:
62:
28:
23:
22:
15:
12:
11:
5:
7509:
7507:
7499:
7498:
7493:
7488:
7483:
7478:
7473:
7463:
7462:
7456:
7455:
7452:
7451:
7449:
7448:
7443:
7434:
7433:
7431:Interleukin 35
7428:
7421:Interleukin 34
7418:
7416:Interleukin 32
7413:
7402:Interleukin 26
7399:
7388:Interleukin 24
7385:
7378:Interleukin 16
7375:
7369:
7367:
7363:
7362:
7360:
7359:
7351:
7349:
7340:
7336:
7335:
7333:
7332:
7323:
7322:
7320:Interleukin 38
7317:
7302:Interleukin 36
7295:
7293:
7287:
7286:
7284:
7283:
7281:Interleukin 33
7274:
7272:
7266:
7265:
7263:
7262:
7260:Interleukin 31
7253:
7251:
7245:
7244:
7242:
7241:
7236:
7225:Interleukin 28
7222:
7213:
7211:
7205:
7204:
7202:
7201:
7192:
7190:
7184:
7183:
7181:
7180:
7175:
7170:
7165:
7160:
7155:
7146:
7145:
7136:
7134:
7128:
7127:
7125:
7124:
7114:
7113:
7111:Interleukin 22
7104:
7102:
7096:
7095:
7093:
7092:
7087:
7078:
7077:
7075:Interleukin 21
7072:
7063:
7061:
7055:
7054:
7052:
7051:
7041:
7040:
7038:Interleukin 24
7035:
7033:Interleukin 20
7030:
7028:Interleukin 19
7021:
7019:
7013:
7012:
7010:
7009:
7000:
6999:
6994:
6992:Interleukin 37
6989:
6987:Interleukin 18
6984:
6975:
6973:
6967:
6966:
6964:
6963:
6958:
6953:
6948:
6943:
6938:
6929:
6928:
6901:Interleukin 17
6894:
6892:
6886:
6885:
6883:
6882:
6880:Interleukin 15
6877:
6868:
6866:
6860:
6859:
6857:
6856:
6851:
6846:
6837:
6836:
6834:Interleukin 13
6831:
6826:
6821:
6812:
6810:
6804:
6803:
6801:
6800:
6795:
6786:
6785:
6783:Interleukin 12
6780:
6771:
6769:
6763:
6762:
6760:
6759:
6754:
6745:
6743:
6737:
6736:
6734:
6733:
6728:
6719:
6717:
6711:
6710:
6708:
6707:
6698:
6697:
6688:
6686:
6680:
6679:
6677:
6676:
6668:
6666:
6660:
6659:
6657:
6656:
6647:
6645:
6639:
6638:
6636:
6635:
6630:
6625:
6620:
6615:
6610:
6605:
6600:
6595:
6590:
6581:
6580:
6575:
6566:
6564:
6558:
6557:
6555:
6554:
6545:
6544:
6539:
6534:
6525:
6524:
6515:
6514:
6505:
6503:
6497:
6496:
6494:
6493:
6488:
6479:
6478:
6469:
6468:
6466:Interleukin 13
6463:
6458:
6449:
6447:
6441:
6440:
6438:
6437:
6435:Promegapoietin
6432:
6427:
6422:
6417:
6412:
6403:
6401:
6395:
6394:
6392:
6391:
6386:
6381:
6372:
6371:
6366:
6361:
6359:Pegaldesleukin
6356:
6351:
6346:
6341:
6336:
6327:
6325:
6319:
6318:
6316:
6315:
6306:
6305:
6300:
6295:
6286:
6285:
6280:
6275:
6270:
6261:
6260:
6255:
6250:
6232:
6230:
6224:
6223:
6215:
6213:
6212:
6205:
6198:
6190:
6181:
6180:
6178:
6177:
6176:
6175:
6174:
6173:
6168:
6163:
6158:
6153:
6143:
6139:
6138:
6137:
6132:
6122:
6113:
6107:
6106:
6105:
6104:
6099:
6086:
6084:
6078:
6077:
6074:
6073:
6071:
6070:
6065:
6060:
6059:
6058:
6053:
6042:
6040:
6036:
6035:
6032:
6031:
6029:
6028:
6013:
6011:
6005:
6004:
6002:
6001:
5996:
5991:
5986:
5981:
5976:
5971:
5966:
5961:
5956:
5951:
5941:
5939:
5937:Ig superfamily
5933:
5932:
5929:
5928:
5925:
5924:
5922:
5921:
5915:
5913:
5907:
5906:
5904:
5903:
5898:
5893:
5888:
5883:
5878:
5873:
5868:
5863:
5858:
5853:
5848:
5843:
5838:
5833:
5828:
5822:
5820:
5811:
5805:
5804:
5802:
5801:
5800:
5799:
5794:
5784:
5779:
5774:
5769:
5764:
5754:
5752:
5743:
5737:
5736:
5733:
5732:
5730:
5729:
5724:
5719:
5714:
5708:
5706:
5702:
5701:
5699:
5698:
5693:
5688:
5683:
5677:
5675:
5665:
5664:
5662:
5661:
5660:
5659:
5654:
5649:
5644:
5633:
5628:
5623:
5618:
5612:
5610:
5603:
5602:
5600:
5599:
5594:
5589:
5583:
5581:
5575:
5574:
5572:
5571:
5566:
5561:
5556:
5547:
5537:
5535:
5526:
5511:
5505:
5504:
5502:
5501:
5496:
5491:
5486:
5481:
5476:
5471:
5466:
5461:
5456:
5451:
5446:
5445:
5444:
5439:
5429:
5423:
5421:
5415:
5414:
5411:
5410:
5408:
5407:
5402:
5396:
5394:
5390:
5389:
5387:
5386:
5380:
5378:
5374:
5373:
5371:
5370:
5365:
5360:
5355:
5350:
5345:
5340:
5335:
5330:
5325:
5320:
5315:
5310:
5305:
5300:
5295:
5290:
5283:
5281:
5277:
5276:
5274:
5273:
5268:
5263:
5258:
5253:
5248:
5243:
5238:
5233:
5228:
5223:
5217:
5212:
5207:
5202:
5197:
5192:
5187:
5182:
5177:
5172:
5167:
5162:
5156:
5150:
5144:
5138:
5132:
5130:
5123:
5114:
5110:
5109:
5102:Cell signaling
5100:
5098:
5097:
5090:
5083:
5075:
5066:
5065:
5063:
5062:
5056:
5049:
5047:
5041:
5034:
5032:
5026:
5019:
5017:
5011:
5004:
5002:
4996:
4989:
4987:
4981:
4974:
4972:
4966:
4959:
4957:
4951:
4944:
4942:
4936:
4929:
4927:
4921:
4914:
4912:
4906:
4899:
4897:
4891:
4884:
4882:
4876:
4869:
4867:
4861:
4854:
4852:
4846:
4839:
4836:
4833:
4832:
4829:
4827:
4826:
4819:
4812:
4804:
4798:
4797:
4776:
4748:(12): 5451–8.
4733:
4721:
4714:
4713:External links
4711:
4709:
4708:
4690:
4672:
4654:
4627:
4608:
4603:New York Times
4589:
4562:(3): 446–514.
4543:
4530:(2): 199–207.
4507:
4501:978-0226701479
4500:
4473:
4424:
4373:
4366:
4345:
4288:
4270:
4251:(4): 295–305.
4234:
4216:
4205:(12): 5241–4.
4189:
4162:
4144:
4101:
4051:
4032:(7): 2268–98.
4016:
3956:
3899:
3847:
3803:
3776:
3750:
3693:
3671:
3665:New York Times
3649:
3608:
3581:(5): 394–422.
3565:
3514:
3473:
3418:
3361:
3318:
3291:(3): 180–190.
3272:
3210:
3167:
3132:Immunogenetics
3115:
3074:
3047:(1): 119–127.
3031:
2973:
2940:Immunogenetics
2930:
2897:Immunogenetics
2886:
2837:
2789:
2740:
2701:(5): 2077–82.
2681:
2646:
2592:
2563:(5): 598–604.
2534:
2471:
2453:
2435:
2414:
2392:
2390:
2387:
2318:
2315:
2263:
2260:
2239:
2236:
2208:
2205:
2191:kidney failure
2167:
2166:
2161:
2152:
2147:
2142:
2133:
2127:
2118:
2080:
2077:
2063:
2060:
2043:
2040:
2023:
2020:
1978:
1975:
1972:
1971:
1969:
1968:
1960:
1958:
1952:
1951:
1949:
1948:
1940:
1938:
1932:
1931:
1929:
1928:
1920:
1918:
1912:
1911:
1909:
1908:
1900:
1898:
1886:
1885:
1883:
1882:
1874:
1872:
1866:
1865:
1861:
1860:
1858:
1857:
1844:
1842:
1836:
1835:
1831:
1830:
1828:
1827:
1814:
1812:
1806:
1805:
1800:
1798:administration
1792:
1791:
1789:
1788:
1770:
1768:
1762:
1761:
1754:
1744:
1743:
1740:
1734:
1733:
1721:
1718:
1705:
1702:
1678:
1675:
1666:feedback loops
1647:
1641:
1633:
1625:
1616:memory T cells
1575:
1572:
1477:heterodimerize
1449:
1446:
1433:
1429:
1421:
1370:
1367:
1361:and activated
1355:IL-2 receptors
1304:
1303:
1300:
1299:
1294:
1284:
1283:
1277:
1276:
1273:
1272:
1270:
1268:
1261:
1260:
1253:
1246:
1242:
1241:
1238:
1237:
1227:
1226:
1220:
1217:
1216:
1206:
1205:
1199:
1195:
1194:
1191:
1190:
1180:
1179:
1173:
1170:
1169:
1159:
1158:
1152:
1148:
1147:
1144:
1143:
1135:
1134:
1128:
1125:
1124:
1116:
1115:
1109:
1103:
1102:
1099:
1098:
1090:
1089:
1083:
1080:
1079:
1071:
1070:
1064:
1058:
1057:
1054:
1053:
1045:
1044:
1038:
1035:
1034:
1026:
1025:
1019:
1013:
1012:
1007:
1002:
998:
997:
987:
986:
983:
982:
971:
970:
968:
967:
962:
957:
952:
947:
942:
937:
932:
927:
922:
917:
912:
907:
902:
897:
892:
887:
882:
877:
872:
867:
862:
857:
852:
847:
842:
837:
832:
827:
822:
817:
812:
807:
802:
797:
792:
787:
782:
777:
772:
767:
762:
757:
751:
749:
745:
744:
742:
741:
736:
731:
725:
723:
719:
718:
716:
715:
710:
705:
700:
695:
690:
685:
680:
674:
672:
668:
667:
657:
656:
653:
652:
649:
648:
640:
639:
628:
622:
621:
618:
617:
609:
608:
605:
604:
602:
601:
597:
593:
589:
585:
581:
577:
573:
569:
565:
561:
558:
557:
546:
543:
542:
540:
539:
535:
531:
527:
523:
519:
515:
511:
507:
503:
499:
496:
495:
483:
482:
474:
463:
457:
456:
453:RNA expression
445:
444:
441:
440:
432:
428:
427:
419:
416:
411:
405:
404:
395:
388:
382:
378:
377:
372:
366:
365:
357:
356:
344:
343:
340:
339:
331:
327:
326:
318:
315:
310:
304:
303:
294:
287:
281:
277:
276:
269:
263:
262:
254:
253:
241:
240:
197:
193:
192:
184:
176:
175:
171:
170:
167:
166:
163:
162:
80:
79:
71:
70:
59:
53:
52:
44:
43:
35:
34:
26:
24:
14:
13:
10:
9:
6:
4:
3:
2:
7508:
7497:
7494:
7492:
7489:
7487:
7484:
7482:
7479:
7477:
7474:
7472:
7469:
7468:
7466:
7447:
7444:
7442:
7439:
7436:
7435:
7432:
7429:
7426:
7422:
7419:
7417:
7414:
7411:
7407:
7403:
7400:
7397:
7393:
7389:
7386:
7383:
7379:
7376:
7374:
7371:
7370:
7368:
7364:
7357:
7353:
7352:
7350:
7348:
7344:
7341:
7337:
7331:
7328:
7325:
7324:
7321:
7318:
7315:
7311:
7307:
7303:
7300:
7297:
7296:
7294:
7292:
7288:
7282:
7279:
7276:
7275:
7273:
7271:
7267:
7261:
7258:
7255:
7254:
7252:
7250:
7246:
7240:
7237:
7234:
7230:
7226:
7223:
7221:
7218:
7215:
7214:
7212:
7210:
7206:
7200:
7197:
7194:
7193:
7191:
7189:
7185:
7179:
7176:
7174:
7173:Tildrakizumab
7171:
7169:
7166:
7164:
7161:
7159:
7156:
7154:
7151:
7148:
7147:
7144:
7141:
7138:
7137:
7135:
7133:
7129:
7122:
7119:
7116:
7115:
7112:
7109:
7106:
7105:
7103:
7101:
7097:
7091:
7088:
7086:
7083:
7080:
7079:
7076:
7073:
7071:
7068:
7065:
7064:
7062:
7060:
7056:
7049:
7046:
7043:
7042:
7039:
7036:
7034:
7031:
7029:
7026:
7023:
7022:
7020:
7018:
7014:
7008:
7005:
7002:
7001:
6998:
6995:
6993:
6990:
6988:
6985:
6983:
6980:
6977:
6976:
6974:
6972:
6968:
6962:
6959:
6957:
6954:
6952:
6949:
6947:
6944:
6942:
6939:
6937:
6934:
6931:
6930:
6926:
6922:
6918:
6914:
6910:
6906:
6902:
6899:
6896:
6895:
6893:
6891:
6887:
6881:
6878:
6876:
6873:
6870:
6869:
6867:
6865:
6861:
6855:
6852:
6850:
6847:
6845:
6842:
6839:
6838:
6835:
6832:
6830:
6829:Interleukin 4
6827:
6825:
6822:
6820:
6817:
6814:
6813:
6811:
6809:
6805:
6799:
6796:
6794:
6791:
6788:
6787:
6784:
6781:
6779:
6778:Edodekin alfa
6776:
6773:
6772:
6770:
6768:
6764:
6758:
6755:
6753:
6750:
6747:
6746:
6744:
6742:
6738:
6732:
6729:
6727:
6724:
6721:
6720:
6718:
6716:
6712:
6706:
6703:
6700:
6699:
6696:
6695:Interleukin 9
6693:
6690:
6689:
6687:
6685:
6681:
6674:
6670:
6669:
6667:
6665:
6661:
6655:
6654:Interleukin 7
6652:
6649:
6648:
6646:
6644:
6640:
6634:
6631:
6629:
6626:
6624:
6621:
6619:
6616:
6614:
6611:
6609:
6606:
6604:
6601:
6599:
6596:
6594:
6591:
6589:
6586:
6583:
6582:
6579:
6578:Interleukin 6
6576:
6574:
6573:Atexakin alfa
6571:
6568:
6567:
6565:
6563:
6559:
6553:
6550:
6547:
6546:
6543:
6540:
6538:
6535:
6533:
6530:
6527:
6526:
6523:
6520:
6517:
6516:
6513:
6512:Interleukin 5
6510:
6507:
6506:
6504:
6502:
6498:
6492:
6489:
6487:
6484:
6481:
6480:
6477:
6474:
6471:
6470:
6467:
6464:
6462:
6461:Interleukin 4
6459:
6457:
6454:
6451:
6450:
6448:
6446:
6442:
6436:
6433:
6431:
6428:
6426:
6423:
6421:
6418:
6416:
6415:Interleukin 3
6413:
6411:
6408:
6405:
6404:
6402:
6400:
6396:
6390:
6387:
6385:
6382:
6380:
6377:
6374:
6373:
6370:
6367:
6365:
6362:
6360:
6357:
6355:
6354:Interleukin 2
6352:
6350:
6347:
6345:
6342:
6340:
6337:
6335:
6332:
6329:
6328:
6326:
6324:
6320:
6314:
6311:
6308:
6307:
6304:
6301:
6299:
6296:
6294:
6291:
6288:
6287:
6284:
6281:
6279:
6276:
6274:
6271:
6269:
6266:
6263:
6262:
6259:
6256:
6254:
6251:
6248:
6244:
6240:
6239:Interleukin 1
6237:
6234:
6233:
6231:
6229:
6225:
6221:
6218:
6211:
6206:
6204:
6199:
6197:
6192:
6191:
6188:
6172:
6169:
6167:
6164:
6162:
6159:
6157:
6154:
6152:
6149:
6148:
6147:
6140:
6136:
6133:
6131:
6128:
6127:
6126:
6119:
6118:
6117:
6114:
6112:
6109:
6108:
6103:
6100:
6098:
6095:
6094:
6093:
6092:
6088:
6087:
6085:
6079:
6069:
6066:
6064:
6061:
6057:
6054:
6052:
6049:
6048:
6047:
6046:Hematopoietic
6044:
6043:
6041:
6037:
6026:
6022:
6018:
6015:
6014:
6012:
6010:
6006:
6000:
5997:
5995:
5992:
5990:
5987:
5985:
5982:
5980:
5977:
5975:
5972:
5970:
5967:
5965:
5962:
5960:
5957:
5955:
5952:
5950:
5946:
5943:
5942:
5940:
5938:
5934:
5920:
5917:
5916:
5914:
5912:
5908:
5902:
5899:
5897:
5894:
5892:
5889:
5887:
5884:
5882:
5879:
5877:
5874:
5872:
5869:
5867:
5864:
5862:
5859:
5857:
5854:
5852:
5849:
5847:
5844:
5842:
5839:
5837:
5834:
5832:
5829:
5827:
5824:
5823:
5821:
5819:
5815:
5812:
5810:
5806:
5798:
5795:
5793:
5790:
5789:
5788:
5785:
5783:
5780:
5778:
5775:
5773:
5770:
5768:
5765:
5763:
5759:
5756:
5755:
5753:
5751:
5747:
5744:
5742:
5738:
5728:
5725:
5723:
5720:
5718:
5715:
5713:
5710:
5709:
5707:
5703:
5697:
5694:
5692:
5689:
5687:
5684:
5682:
5679:
5678:
5676:
5674:
5670:
5666:
5658:
5655:
5653:
5650:
5648:
5645:
5643:
5639:
5638:
5637:
5634:
5632:
5629:
5627:
5624:
5622:
5619:
5617:
5614:
5613:
5611:
5609:
5604:
5598:
5595:
5593:
5590:
5588:
5585:
5584:
5582:
5580:
5576:
5570:
5567:
5565:
5562:
5560:
5557:
5555:
5551:
5548:
5546:
5542:
5539:
5538:
5536:
5534:
5530:
5527:
5519:
5515:
5512:
5510:
5506:
5500:
5497:
5495:
5492:
5490:
5487:
5485:
5482:
5480:
5477:
5475:
5472:
5470:
5467:
5465:
5462:
5460:
5457:
5455:
5454:TNFSF5/CD40LG
5452:
5450:
5447:
5443:
5440:
5438:
5435:
5434:
5433:
5430:
5428:
5425:
5424:
5422:
5420:
5416:
5406:
5403:
5401:
5398:
5397:
5395:
5391:
5385:
5382:
5381:
5379:
5375:
5369:
5366:
5364:
5361:
5359:
5356:
5354:
5351:
5349:
5346:
5344:
5341:
5339:
5336:
5334:
5331:
5329:
5326:
5324:
5321:
5319:
5316:
5314:
5311:
5309:
5306:
5304:
5301:
5299:
5296:
5294:
5291:
5288:
5285:
5284:
5282:
5278:
5272:
5269:
5267:
5264:
5262:
5259:
5257:
5254:
5252:
5249:
5247:
5244:
5242:
5239:
5237:
5234:
5232:
5229:
5227:
5224:
5221:
5218:
5216:
5213:
5211:
5208:
5206:
5203:
5201:
5198:
5196:
5193:
5191:
5188:
5186:
5183:
5181:
5178:
5176:
5173:
5171:
5168:
5166:
5163:
5160:
5157:
5154:
5151:
5148:
5145:
5142:
5139:
5137:
5134:
5133:
5131:
5127:
5124:
5122:
5118:
5115:
5111:
5107:
5103:
5096:
5091:
5089:
5084:
5082:
5077:
5076:
5073:
5059:
5053:
5048:
5044:
5038:
5033:
5029:
5023:
5018:
5014:
5008:
5003:
4999:
4993:
4988:
4984:
4978:
4973:
4969:
4963:
4958:
4954:
4948:
4943:
4939:
4933:
4928:
4924:
4918:
4913:
4909:
4903:
4898:
4894:
4888:
4883:
4879:
4873:
4868:
4864:
4858:
4853:
4849:
4843:
4838:
4834:
4825:
4820:
4818:
4813:
4811:
4806:
4805:
4802:
4795:
4791:
4790:
4785:
4781:
4777:
4773:
4769:
4764:
4759:
4755:
4751:
4747:
4743:
4739:
4734:
4732:
4728:
4725:
4722:
4720:
4717:
4716:
4712:
4704:
4700:
4694:
4691:
4686:
4682:
4676:
4673:
4668:
4664:
4658:
4655:
4650:
4646:
4642:
4638:
4631:
4628:
4623:
4619:
4612:
4609:
4604:
4600:
4593:
4590:
4585:
4581:
4577:
4573:
4569:
4565:
4561:
4557:
4550:
4548:
4544:
4538:
4533:
4529:
4525:
4518:
4511:
4508:
4503:
4497:
4492:
4491:
4482:
4480:
4478:
4474:
4469:
4465:
4460:
4455:
4451:
4447:
4444:(2): 454–64.
4443:
4439:
4435:
4428:
4425:
4420:
4416:
4412:
4408:
4404:
4400:
4396:
4392:
4388:
4384:
4377:
4374:
4369:
4363:
4359:
4352:
4350:
4346:
4341:
4337:
4333:
4329:
4324:
4319:
4315:
4311:
4307:
4303:
4299:
4292:
4289:
4286:
4282:
4281:
4274:
4271:
4266:
4262:
4258:
4254:
4250:
4246:
4238:
4235:
4230:
4226:
4220:
4217:
4212:
4208:
4204:
4200:
4193:
4190:
4185:
4181:
4177:
4173:
4166:
4163:
4158:
4154:
4148:
4145:
4140:
4136:
4132:
4128:
4124:
4120:
4116:
4112:
4105:
4102:
4096:
4091:
4087:
4083:
4078:
4073:
4069:
4065:
4061:
4055:
4052:
4047:
4043:
4039:
4035:
4031:
4027:
4020:
4017:
4012:
4008:
4004:
4000:
3995:
3990:
3986:
3982:
3978:
3974:
3970:
3963:
3961:
3957:
3952:
3948:
3944:
3940:
3935:
3930:
3926:
3922:
3919:(7): 931–50.
3918:
3914:
3910:
3903:
3900:
3895:
3891:
3886:
3881:
3877:
3873:
3870:(7): 931–50.
3869:
3865:
3861:
3854:
3852:
3848:
3843:
3839:
3834:
3829:
3826:(4): 645–54.
3825:
3821:
3817:
3810:
3808:
3804:
3800:
3796:
3793:
3787:
3785:
3783:
3781:
3777:
3765:
3761:
3754:
3751:
3746:
3742:
3737:
3732:
3728:
3724:
3720:
3716:
3712:
3708:
3704:
3697:
3694:
3689:
3685:
3681:
3675:
3672:
3666:
3663:
3656:
3654:
3650:
3645:
3641:
3636:
3631:
3628:(6): 488–96.
3627:
3623:
3619:
3612:
3609:
3604:
3600:
3596:
3592:
3588:
3584:
3580:
3576:
3569:
3566:
3561:
3557:
3552:
3547:
3542:
3537:
3533:
3529:
3525:
3518:
3515:
3510:
3506:
3501:
3496:
3492:
3488:
3484:
3477:
3474:
3469:
3465:
3460:
3455:
3450:
3445:
3441:
3437:
3433:
3431:
3422:
3419:
3414:
3410:
3406:
3402:
3397:
3392:
3388:
3384:
3380:
3376:
3372:
3365:
3362:
3357:
3353:
3349:
3345:
3341:
3337:
3333:
3329:
3322:
3319:
3314:
3310:
3306:
3302:
3298:
3294:
3290:
3286:
3279:
3277:
3273:
3268:
3264:
3259:
3254:
3249:
3244:
3240:
3236:
3232:
3228:
3224:
3217:
3215:
3211:
3206:
3202:
3198:
3194:
3190:
3186:
3182:
3178:
3171:
3168:
3163:
3159:
3154:
3149:
3145:
3141:
3138:(2): 93–103.
3137:
3133:
3129:
3122:
3120:
3116:
3111:
3107:
3102:
3097:
3093:
3089:
3085:
3078:
3075:
3070:
3066:
3062:
3058:
3054:
3050:
3046:
3042:
3035:
3032:
3027:
3023:
3018:
3013:
3008:
3003:
2999:
2995:
2991:
2984:
2982:
2980:
2978:
2974:
2969:
2965:
2961:
2957:
2953:
2949:
2945:
2941:
2934:
2931:
2926:
2922:
2918:
2914:
2910:
2906:
2902:
2898:
2890:
2887:
2882:
2878:
2873:
2868:
2864:
2860:
2857:(2): 153–65.
2856:
2852:
2848:
2841:
2838:
2833:
2829:
2825:
2821:
2817:
2813:
2809:
2805:
2804:
2796:
2794:
2790:
2785:
2781:
2776:
2771:
2767:
2763:
2759:
2755:
2751:
2744:
2741:
2736:
2732:
2727:
2722:
2717:
2712:
2708:
2704:
2700:
2696:
2692:
2685:
2682:
2677:
2673:
2669:
2665:
2662:(3): 109–23.
2661:
2657:
2650:
2647:
2642:
2638:
2634:
2630:
2626:
2622:
2618:
2614:
2610:
2606:
2599:
2597:
2593:
2588:
2584:
2579:
2574:
2570:
2566:
2562:
2558:
2554:
2547:
2545:
2543:
2541:
2539:
2535:
2530:
2526:
2522:
2518:
2514:
2510:
2506:
2502:
2495:
2488:
2486:
2484:
2482:
2480:
2478:
2476:
2472:
2467:
2463:
2457:
2454:
2449:
2445:
2439:
2436:
2432:
2428:
2423:
2421:
2419:
2415:
2411:
2407:
2402:
2400:
2398:
2394:
2388:
2386:
2384:
2379:
2375:
2371:
2366:
2364:
2360:
2356:
2351:
2347:
2343:
2338:
2336:
2332:
2328:
2323:
2316:
2314:
2312:
2308:
2304:
2300:
2296:
2292:
2287:
2283:
2279:
2278:
2273:
2269:
2261:
2259:
2255:
2253:
2249:
2244:
2237:
2235:
2233:
2229:
2225:
2221:
2217:
2213:
2206:
2204:
2201:
2198:
2196:
2192:
2188:
2184:
2180:
2176:
2172:
2165:
2162:
2160:
2156:
2153:
2151:
2148:
2146:
2143:
2141:
2137:
2134:
2132:
2128:
2126:
2122:
2119:
2116:
2112:
2108:
2104:
2100:
2096:
2093:
2092:
2091:
2088:
2086:
2078:
2076:
2072:
2068:
2061:
2059:
2056:
2054:
2048:
2042:United States
2041:
2039:
2035:
2033:
2029:
2028:United States
2021:
2019:
2016:
2014:
2009:
2007:
2003:
1999:
1996:(FDA) with a
1995:
1991:
1987:
1983:
1976:
1966:
1965:ChEMBL1201438
1962:
1961:
1959:
1957:
1953:
1946:
1942:
1941:
1939:
1937:
1933:
1926:
1922:
1921:
1919:
1917:
1913:
1906:
1902:
1901:
1899:
1891:
1887:
1880:
1876:
1875:
1873:
1871:
1867:
1862:
1856:
1846:
1845:
1843:
1841:
1837:
1832:
1824:
1819:
1816:
1815:
1813:
1811:
1807:
1804:
1801:
1799:
1793:
1786:
1781:
1772:
1771:
1769:
1767:
1763:
1759:
1755:
1753:
1749:
1745:
1741:
1739:
1735:
1732:Clinical data
1730:
1719:
1717:
1715:
1711:
1703:
1701:
1698:
1695:
1692:
1686:
1684:
1676:
1674:
1672:
1667:
1662:
1660:
1656:
1651:
1650:lymphocytes.
1645:
1637:
1629:
1621:
1617:
1613:
1609:
1605:
1601:
1597:
1593:
1589:
1585:
1581:
1573:
1571:
1569:
1565:
1563:
1559:
1557:
1553:
1551:
1547:
1542:
1540:
1536:
1532:
1526:
1524:
1520:
1516:
1515:PI3K/Akt/mTOR
1512:
1508:
1504:
1500:
1496:
1493:
1492:phosphorylate
1489:
1485:
1482:
1481:Janus kinases
1478:
1475:
1471:
1467:
1463:
1462:PI3K/Akt/mTOR
1459:
1455:
1447:
1445:
1443:
1439:
1427:
1418:
1416:
1412:
1408:
1404:
1400:
1399:IL-2 receptor
1396:
1392:
1388:
1384:
1380:
1376:
1369:IL-2 receptor
1368:
1366:
1364:
1360:
1356:
1352:
1349:
1345:
1341:
1337:
1333:
1330:
1326:
1325:immune system
1322:
1318:
1314:
1310:
1309:Interleukin-2
1298:
1293:
1289:
1285:
1282:
1278:
1271:
1269:
1266:
1262:
1258:
1254:
1251:
1247:
1243:
1236:
1234:
1228:
1224:
1221:
1215:
1213:
1207:
1203:
1200:
1196:
1189:
1187:
1181:
1177:
1174:
1168:
1166:
1160:
1156:
1153:
1151:RefSeq (mRNA)
1149:
1142:
1141:
1136:
1132:
1129:
1123:
1122:
1117:
1113:
1110:
1108:
1104:
1097:
1096:
1091:
1087:
1084:
1078:
1077:
1072:
1068:
1065:
1063:
1059:
1052:
1051:
1046:
1042:
1039:
1033:
1032:
1027:
1023:
1020:
1018:
1014:
1011:
1008:
1006:
1003:
999:
996:
992:
988:
981:
977:
972:
966:
963:
961:
958:
956:
953:
951:
948:
946:
943:
941:
938:
936:
933:
931:
928:
926:
923:
921:
918:
916:
913:
911:
908:
906:
903:
901:
898:
896:
893:
891:
888:
886:
883:
881:
878:
876:
873:
871:
868:
866:
863:
861:
860:cell adhesion
858:
856:
853:
851:
848:
846:
843:
841:
838:
836:
833:
831:
828:
826:
823:
821:
818:
816:
813:
811:
808:
806:
803:
801:
798:
796:
793:
791:
788:
786:
783:
781:
778:
776:
773:
771:
768:
766:
763:
761:
758:
756:
753:
752:
750:
747:
746:
740:
737:
735:
732:
730:
727:
726:
724:
721:
720:
714:
711:
709:
706:
704:
701:
699:
696:
694:
691:
689:
686:
684:
681:
679:
676:
675:
673:
670:
669:
666:
665:Gene ontology
662:
658:
646:
641:
637:
632:
629:
627:
623:
615:
610:
599:
595:
591:
587:
583:
579:
575:
571:
567:
563:
562:
559:
555:
550:
547:
537:
533:
529:
525:
521:
517:
513:
509:
505:
501:
500:
497:
493:
488:
485:
484:
481:
479:
475:
473:
472:
468:
467:
464:
462:
458:
454:
450:
446:
438:
433:
429:
425:
420:
410:
406:
399:
392:
386:
379:
371:
367:
363:
358:
354:
349:
345:
337:
332:
328:
324:
319:
309:
305:
298:
291:
285:
278:
274:
268:
264:
260:
255:
251:
246:
242:
238:
234:
230:
226:
222:
218:
214:
210:
206:
202:
194:
189:
182:
177:
172:
161:
159:
155:
151:
147:
143:
139:
135:
131:
127:
123:
119:
115:
111:
107:
103:
99:
95:
91:
87:
81:
76:
73:
72:
68:
65:
58:
54:
49:
45:
41:
36:
31:
19:
7476:Interleukins
7437:
7425:M-CSFR/CSF1R
7412:heterodimer)
7398:heterodimer)
7327:Antagonists:
7326:
7298:
7277:
7256:
7216:
7195:
7168:Risankizumab
7149:
7139:
7117:
7107:
7090:NNC0114-0006
7085:NNC0114-0005
7081:
7066:
7044:
7024:
7003:
6978:
6932:
6897:
6871:
6854:Tralokinumab
6849:Lebrikizumab
6844:Anrukinzumab
6840:
6815:
6789:
6774:
6748:
6722:
6701:
6691:
6650:
6593:Clazakizumab
6584:
6569:
6548:
6532:Benralizumab
6528:
6519:Antagonists:
6518:
6508:
6491:Pascolizumab
6482:
6473:Antagonists:
6472:
6452:
6406:
6375:
6353:
6330:
6309:
6289:
6265:Antagonists:
6264:
6235:
6141:
6120:
6089:
6081:By function/
5792:IL28/IFNL2+3
5540:
5057:
5042:
5027:
5012:
4997:
4982:
4967:
4952:
4937:
4922:
4907:
4892:
4877:
4862:
4847:
4787:
4745:
4741:
4703:Pharmaletter
4702:
4693:
4684:
4675:
4666:
4657:
4640:
4636:
4630:
4621:
4611:
4602:
4592:
4559:
4555:
4527:
4523:
4510:
4489:
4441:
4437:
4427:
4389:(1): 14–27.
4386:
4382:
4376:
4357:
4305:
4301:
4291:
4278:
4273:
4248:
4244:
4237:
4229:News Release
4228:
4219:
4202:
4198:
4192:
4175:
4171:
4165:
4156:
4147:
4114:
4110:
4104:
4067:
4063:
4054:
4029:
4025:
4019:
3979:(8): 792–8.
3976:
3972:
3916:
3912:
3902:
3867:
3863:
3823:
3819:
3767:. Retrieved
3763:
3753:
3710:
3706:
3696:
3688:the original
3683:
3674:
3664:
3625:
3621:
3611:
3578:
3574:
3568:
3531:
3527:
3517:
3490:
3486:
3476:
3439:
3435:
3429:
3421:
3378:
3374:
3364:
3334:(1): 35–44.
3331:
3327:
3321:
3288:
3284:
3230:
3226:
3180:
3176:
3170:
3135:
3131:
3091:
3087:
3077:
3044:
3040:
3034:
2997:
2993:
2946:(1): 35–51.
2943:
2939:
2933:
2900:
2896:
2889:
2854:
2850:
2840:
2807:
2801:
2760:(1): 13–25.
2757:
2753:
2743:
2698:
2694:
2684:
2659:
2655:
2649:
2608:
2604:
2560:
2556:
2504:
2500:
2465:
2456:
2447:
2438:
2367:
2339:
2324:
2320:
2281:
2275:
2265:
2256:
2245:
2241:
2210:
2202:
2199:
2168:
2089:
2082:
2073:
2069:
2065:
2057:
2053:chemotherapy
2049:
2045:
2036:
2032:side effects
2025:
2017:
2010:
1980:
1840:Legal status
1834:Legal status
1766:License data
1707:
1699:
1696:
1687:
1680:
1663:
1652:
1577:
1567:
1566:
1561:
1560:
1555:
1554:
1543:
1527:
1507:cell nucleus
1451:
1419:
1372:
1319:, a type of
1312:
1308:
1307:
1230:
1209:
1183:
1162:
1138:
1119:
1093:
1074:
1048:
1029:
1009:
1004:
835:MAPK cascade
596:spermatocyte
476:
469:
334:122,456,725
321:122,451,470
196:External IDs
83:
7178:Ustekinumab
7158:Briakinumab
7150:Antibodies:
7121:Fezakinumab
7118:Antibodies:
7082:Antibodies:
7070:Denenicokin
7045:Antibodies:
6982:Iboctadekin
6961:Vunakizumab
6956:Secukinumab
6946:Perakizumab
6933:Antibodies:
6841:Antibodies:
6798:Ustekinumab
6793:Briakinumab
6790:Antibodies:
6702:Antibodies:
6628:Tocilizumab
6598:Elsilimomab
6585:Antibodies:
6537:Mepolizumab
6529:Antibodies:
6483:Antibodies:
6410:Daniplestim
6379:Basiliximab
6376:Antibodies:
6344:Celmoleukin
6339:Aldesleukin
6303:Lutikizumab
6298:Gevokizumab
6293:Canakinumab
6290:Antibodies:
6009:IL17 family
5750:IL10 family
5669:IL12 family
5521:(grouped by
5509:Interleukin
5432:Lymphotoxin
4830:PDB gallery
4280:NCT03113773
3769:February 1,
2331:bone marrow
2295:CD8 T cells
2293:and memory
1982:Aldesleukin
1879:110942-02-4
1864:Identifiers
1803:Intravenous
1785:aldesleukin
1738:Trade names
1726:Aldesleukin
1720:Medical use
1363:CD8 T cells
1359:CD4 T cells
1340:lymphocytes
1317:interleukin
530:gallbladder
518:granulocyte
435:37,180,108
422:37,174,672
174:Identifiers
7496:Immunology
7465:Categories
7233:B (IFN-λ3)
7229:A (IFN-λ2)
7163:Guselkumab
7153:Brazikumab
7048:Fletikumab
6951:Remtolumab
6941:Ixekizumab
6936:Brodalumab
6819:Binetrakin
6757:Oprelvekin
6726:Ilodecakin
6705:Enokizumab
6618:Siltuximab
6608:Olokizumab
6542:Reslizumab
6476:Pitrakinra
6456:Binetrakin
6425:Milodistim
6420:Leridistim
6389:Inolimomab
6364:Teceleukin
6283:Isunakinra
6220:modulators
6116:Lymphokine
5954:IL1B/IL1F2
5949:IL1A/IL1F1
5945:IL1 family
5809:Interferon
5797:IL29/IFNL1
3183:: 103895.
3000:: 549319.
2433:, May 2017
2412:, May 2017
2389:References
2374:methionine
2327:lymphocyte
2189:problems,
2175:infections
2155:drowsiness
2111:joint pain
1945:M89N0Q7EQR
1870:CAS Number
1683:IL-15-like
1525:pathway).
1440:, whereas
592:blastocyst
538:right lung
510:lymph node
480:(ortholog)
217:HomoloGene
7438:Unsorted:
7299:Agonists:
7278:Agonists:
7257:Agonists:
7217:Agonists:
7196:Agonists:
7140:Agonists:
7108:Agonists:
7067:Agonists:
7025:Agonists:
6997:Tadekinig
6979:Agonists:
6898:Agonists:
6872:Agonists:
6816:Agonists:
6775:Agonists:
6749:Agonists:
6723:Agonists:
6692:Agonists:
6651:Agonists:
6633:Levilimab
6623:Sirukumab
6613:Sarilumab
6570:Agonists:
6509:Agonists:
6486:Dupilumab
6453:Agonists:
6430:Muplestim
6407:Agonists:
6331:Agonists:
6258:Pifonakin
6253:Mobenakin
6236:Agonists:
5994:33/IL1F11
5959:1Ra/IL1F3
5606:IL6 like/
5323:CXCL8/IL8
5121:Chemokine
5113:By family
5106:cytokines
4667:KEGG drug
4584:209143485
4139:195358361
4086:0027-8424
3205:223557924
2968:231770873
2365:in 1992.
2171:breathing
2159:confusion
1796:Routes of
1758:Monograph
1752:Drugs.com
1742:Proleukin
1714:psoriasis
1710:itchiness
1677:Evolution
1614:and into
1590:. In the
1580:tolerance
1405:), beta (
1351:infection
1348:microbial
1233:NP_032392
1212:NP_000577
1186:NM_008366
1165:NM_000586
995:Orthologs
580:esophagus
568:spermatid
225:GeneCards
18:Proleukin
7392:IL-22Rα1
7358:instead.
6675:instead.
6603:mAb 1339
6588:ARGX-109
6552:TPI ASM8
6522:YM-90709
6273:Anakinra
6268:AF-12198
6111:Monokine
5640:+non IL
5525:subunit)
5523:receptor
5494:TNFSF13B
5442:TNFC/LTB
5437:TNFB/LTA
4772:24907378
4727:Archived
4649:12469934
4637:Oncology
4411:20074271
4340:42880544
4332:16484453
4265:24622415
4211:20044643
4184:16827142
4131:11702307
4046:19009549
4011:41522233
4003:15685449
3994:11033014
3951:41522233
3943:15685449
3934:11033014
3894:18256831
3842:26259990
3795:Archived
3764:BioSpace
3745:30626941
3644:19544689
3622:Oncology
3603:34226322
3595:18031103
3575:BioDrugs
3560:18288273
3509:11390392
3468:30093902
3442:: 1683.
3413:22936159
3405:21063894
3396:11115099
3356:22051181
3313:22680847
3305:22343569
3267:20133667
3197:33065202
3162:24276591
3069:17101279
3026:33193315
2960:33512550
2917:15592926
2881:20732639
2851:Immunity
2832:51939991
2824:30089912
2784:23352221
2754:Immunity
2676:15473953
2656:Cytokine
2641:85394260
2633:16293754
2587:21889323
2521:26572555
2429:–
2408:–
2383:Novartis
2291:NK cells
2286:cytokine
2234:(CTCL).
2222:and the
2179:seizures
2145:diarrhea
2136:weakness
2125:vomiting
2103:headache
2079:Toxicity
1916:DrugBank
1905:46508054
1810:ATC code
1780:DailyMed
1584:immunity
1574:Function
1523:MAPK/ERK
1519:JAK-STAT
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