Gene Symbol: Il21r
Description: interleukin 21 receptor
Alias: NILR, interleukin-21 receptor, IL-21 receptor, IL-21R, LR-beta, NR8, lymphocyte receptor beta, novel cytokine receptor 8, novel interleukin receptor
Species: mouse
Products:     Il21r

Top Publications

  1. Kasaian M, Whitters M, Carter L, Lowe L, Jussif J, Deng B, et al. IL-21 limits NK cell responses and promotes antigen-specific T cell activation: a mediator of the transition from innate to adaptive immunity. Immunity. 2002;16:559-69 pubmed
    ..These observations suggest that IL-21 promotes the transition between innate and adaptive immunity. ..
  2. Jin H, Carrio R, Yu A, Malek T. Distinct activation signals determine whether IL-21 induces B cell costimulation, growth arrest, or Bim-dependent apoptosis. J Immunol. 2004;173:657-65 pubmed
    ..We favor a model in which IL-21 promotes B cell maturation during a productive T cell-dependent B cell response, while favoring growth arrest and apoptosis for nonspecifically or inappropriately activated B cells. ..
  3. Suto A, Kashiwakuma D, Kagami S, Hirose K, Watanabe N, Yokote K, et al. Development and characterization of IL-21-producing CD4+ T cells. J Exp Med. 2008;205:1369-79 pubmed publisher
  4. Jang E, Cho S, Park H, Paik D, Kim J, Youn J. A positive feedback loop of IL-21 signaling provoked by homeostatic CD4+CD25- T cell expansion is essential for the development of arthritis in autoimmune K/BxN mice. J Immunol. 2009;182:4649-56 pubmed publisher
    ..Our findings suggest that effective targeting of IL-21-mediated processes may be useful in treating autoimmune arthritis. ..
  5. Oh I, Ozaki K, Meguro A, Hatanaka K, Kadowaki M, Matsu H, et al. Altered effector CD4+ T cell function in IL-21R-/- CD4+ T cell-mediated graft-versus-host disease. J Immunol. 2010;185:1920-6 pubmed publisher
    ..Thus, the attenuated GVHD might be caused by an impairment of effector T cell differentiation itself, rather than by an increase in regulatory T cells and suppression of effector T cells. ..
  6. Ozaki K, Spolski R, Feng C, Qi C, Cheng J, Sher A, et al. A critical role for IL-21 in regulating immunoglobulin production. Science. 2002;298:1630-4 pubmed
    ..This suggests that these gammac-dependent cytokines may be those whose inactivation is primarily responsible for the B cell defect in humans with XSCID. ..
  7. Spolski R, Kashyap M, Robinson C, Yu Z, Leonard W. IL-21 signaling is critical for the development of type I diabetes in the NOD mouse. Proc Natl Acad Sci U S A. 2008;105:14028-33 pubmed publisher
    ..To determine the role of IL-21 in diabetes, Il21r-knockout (KO) mice were backcrossed to NOD mice...
  8. Novy P, Huang X, Leonard W, Yang Y. Intrinsic IL-21 signaling is critical for CD8 T cell survival and memory formation in response to vaccinia viral infection. J Immunol. 2011;186:2729-38 pubmed publisher
    ..These results identify a critical role for intrinsic IL-21 signaling in CD8 T cell responses to an acute viral infection in vivo and may help design effective vaccine strategies. ..
  9. Attridge K, Wang C, Wardzinski L, Kenefeck R, Chamberlain J, Manzotti C, et al. IL-21 inhibits T cell IL-2 production and impairs Treg homeostasis. Blood. 2012;119:4656-64 pubmed publisher
    ..The data also suggest a new paradigm whereby cytokines can promote immunity by inhibiting IL-2. ..

More Information


  1. Sutherland A, Van Belle T, Wurster A, Suto A, Michaud M, Zhang D, et al. Interleukin-21 is required for the development of type 1 diabetes in NOD mice. Diabetes. 2009;58:1144-55 pubmed publisher
  2. Linterman M, Beaton L, Yu D, Ramiscal R, Srivastava M, Hogan J, et al. IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center responses. J Exp Med. 2010;207:353-63 pubmed publisher
    ..In contrast to the requirement for IL-21 in the follicular response to sheep red blood cells, a purely extrafollicular antibody response to Salmonella dominated by IgG2a was intact in the absence of IL-21...
  3. Parrish Novak J, Dillon S, Nelson A, Hammond A, Sprecher C, Gross J, et al. Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Nature. 2000;408:57-63 pubmed
  4. Yi J, Du M, Zajac A. A vital role for interleukin-21 in the control of a chronic viral infection. Science. 2009;324:1572-6 pubmed publisher
    ..Thus, IL-21 serves as a critical helper factor that shapes the functional quality of antiviral CD8+ T cells and is required for viral control. ..
  5. Habib T, Senadheera S, Weinberg K, Kaushansky K. The common gamma chain (gamma c) is a required signaling component of the IL-21 receptor and supports IL-21-induced cell proliferation via JAK3. Biochemistry. 2002;41:8725-31 pubmed
  6. Rankin A, MacLeod H, Keegan S, Andreyeva T, Lowe L, Bloom L, et al. IL-21 receptor is critical for the development of memory B cell responses. J Immunol. 2011;186:667-74 pubmed publisher
    ..KO mice, and consequently, secondary IgG Ab responses to NP hapten conjugated to chicken ? globulin were significantly impaired. These results identify the IL-21 pathway as a critical component of the memory B cell response. ..
  7. Kashiwakuma D, Suto A, Hiramatsu Y, Ikeda K, Takatori H, Suzuki K, et al. B and T lymphocyte attenuator suppresses IL-21 production from follicular Th cells and subsequent humoral immune responses. J Immunol. 2010;185:2730-6 pubmed publisher
    ..These results suggest that BTLA signaling suppresses IL-21 production from Tfh cells and subsequent Tfh cell-mediated IgG responses. ..
  8. Sonderegger I, Kisielow J, Meier R, King C, Kopf M. IL-21 and IL-21R are not required for development of Th17 cells and autoimmunity in vivo. Eur J Immunol. 2008;38:1833-8 pubmed publisher
    ..CD4 T cells, their recruitment to inflamed organs, and the development of autoimmune disease was not affected in il21R(-/-) and il21(-/-) mice in models of myelin oligodendrocyte glycoprotein-induced autoimmune encephalitis and ..
  9. Zotos D, Coquet J, Zhang Y, Light A, D Costa K, Kallies A, et al. IL-21 regulates germinal center B cell differentiation and proliferation through a B cell-intrinsic mechanism. J Exp Med. 2010;207:365-78 pubmed publisher
    ..The absence of IL-21 or IL-21 receptor does not abrogate the appearance of T cells in GCs or the appearance of CD4 T cells with a follicular helper phenotype. IL-21 thus controls fate choices of GC B cells directly...
  10. Bucher C, Koch L, Vogtenhuber C, Goren E, Munger M, Panoskaltsis Mortari A, et al. IL-21 blockade reduces graft-versus-host disease mortality by supporting inducible T regulatory cell generation. Blood. 2009;114:5375-84 pubmed publisher
    ..Together, these data indicate that IL-21 suppresses inducible Treg conversion and further suggest that IL-21 blockade is an attractive strategy to reduce GVHD-induced injury. ..
  11. Rasheed M, Latner D, Aubert R, Gourley T, Spolski R, Davis C, et al. Interleukin-21 is a critical cytokine for the generation of virus-specific long-lived plasma cells. J Virol. 2013;87:7737-46 pubmed publisher
    ..Taken together, our results highlight the importance of IL-21 in humoral immunity to viruses...
  12. Fröhlich A, Marsland B, Sonderegger I, Kurrer M, Hodge M, Harris N, et al. IL-21 receptor signaling is integral to the development of Th2 effector responses in vivo. Blood. 2007;109:2023-31 pubmed
    ..Overall, our data show IL-21 plays a crucial role in supporting polarized Th2 responses in vivo, while appearing superfluous for Th1 and Th17 responses. ..
  13. Zeng R, Spolski R, Finkelstein S, Oh S, Kovanen P, Hinrichs C, et al. Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function. J Exp Med. 2005;201:139-48 pubmed
    ..Thus, our studies reveal that IL-21 potently regulates CD8+ T cell expansion and effector function, primarily in a synergistic context with IL-15. ..
  14. Coquet J, Chakravarti S, Smyth M, Godfrey D. Cutting edge: IL-21 is not essential for Th17 differentiation or experimental autoimmune encephalomyelitis. J Immunol. 2008;180:7097-101 pubmed
    ..Thus, our results challenge the notion that IL-21 is a key factor in driving Th17 immunity and disease. ..
  15. King I, Mohrs K, Mohrs M. A nonredundant role for IL-21 receptor signaling in plasma cell differentiation and protective type 2 immunity against gastrointestinal helminth infection. J Immunol. 2010;185:6138-45 pubmed publisher
    ..Our studies demonstrate a selective role for IL-21 in plasma cell differentiation in the context of protective antiparasitic type 2 immunity...
  16. Barker B, Gladstone M, Gillard G, Panas M, Letvin N. Critical role for IL-21 in both primary and memory anti-viral CD8+ T-cell responses. Eur J Immunol. 2010;40:3085-96 pubmed publisher
    ..These findings indicate that IL-21 is an important mediator of CD4(+) T-cell help to CD8(+) T cells. ..
  17. McGuire H, Walters S, Vogelzang A, Lee C, Webster K, Sprent J, et al. Interleukin-21 is critically required in autoimmune and allogeneic responses to islet tissue in murine models. Diabetes. 2011;60:867-75 pubmed publisher
    ..These findings suggest that therapeutic manipulation of IL-21 may serve as a suitable treatment for patients with type 1 diabetes. ..
  18. Datta S, SARVETNICK N. IL-21 limits peripheral lymphocyte numbers through T cell homeostatic mechanisms. PLoS ONE. 2008;3:e3118 pubmed publisher
    ..Taken together, our results suggest that IL-21 plays a global role in regulating T cell homeostasis, promoting the continuous adaptation of the T cell lymphoid space. ..
  19. Hanash A, Kappel L, Yim N, Nejat R, Goldberg G, Smith O, et al. Abrogation of donor T-cell IL-21 signaling leads to tissue-specific modulation of immunity and separation of GVHD from GVL. Blood. 2011;118:446-55 pubmed publisher
    ..IL-21 is thus an exciting target for therapeutic intervention and improvement of clinical transplantation outcomes. ..
  20. Fröhlich A, Kisielow J, Schmitz I, Freigang S, Shamshiev A, Weber J, et al. IL-21R on T cells is critical for sustained functionality and control of chronic viral infection. Science. 2009;324:1576-80 pubmed publisher
    Chronic viral infection is often associated with the dysfunction of virus-specific T cells. Our studies using Il21r-deficient (Il21r-/-) mice now suggest that interleukin-21 (IL-21) is critical for the long-term maintenance and ..
  21. Wang L, Yu C, Kim H, Liao W, Telford W, Egwuagu C, et al. Key role for IL-21 in experimental autoimmune uveitis. Proc Natl Acad Sci U S A. 2011;108:9542-7 pubmed publisher
    ..Furthermore, Il21r(-/-) mice were more resistant to EAU development than wild-type mice, and adoptive transfer of Il21r(-/-) T cells ..
  22. Hiramatsu Y, Suto A, Kashiwakuma D, Kanari H, Kagami S, Ikeda K, et al. c-Maf activates the promoter and enhancer of the IL-21 gene, and TGF-beta inhibits c-Maf-induced IL-21 production in CD4+ T cells. J Leukoc Biol. 2010;87:703-12 pubmed publisher
    ..Taken together, these results suggest that c-Maf induces IL-21 production directly in CD4(+) T cells by activating IL-21P and the CNS-2 enhancer and that TGF-beta suppresses c-Maf-induced IL-21 production in CD4(+) T cells. ..
  23. Spolski R, Kim H, Zhu W, Levy D, Leonard W. IL-21 mediates suppressive effects via its induction of IL-10. J Immunol. 2009;182:2859-67 pubmed publisher
    ..Overall, our data indicate that IL-21 regulates immune responses at least in part by inducing IL-10 and reveal unanticipated immunosuppressive actions for this cytokine. ..
  24. Vogelzang A, McGuire H, Yu D, Sprent J, Mackay C, King C. A fundamental role for interleukin-21 in the generation of T follicular helper cells. Immunity. 2008;29:127-37 pubmed publisher
    ..This study reveals a previously unappreciated role for Tfh cells in the formation of the GC and isotype switching through a CD4(+) T cell-intrinsic requirement for IL-21. ..
  25. Zhou L, Ivanov I, Spolski R, Min R, Shenderov K, Egawa T, et al. IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol. 2007;8:967-74 pubmed
    ..IL-6 therefore orchestrates a series of 'downstream' cytokine-dependent signaling pathways that, in concert with TGF-beta, amplify RORgammat-dependent differentiation of T(H)-17 cells. ..
  26. Korn T, Bettelli E, Gao W, Awasthi A, Jäger A, Strom T, et al. IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature. 2007;448:484-487 pubmed publisher
    ..We show that an IL-2 cytokine family member, IL-21, cooperates with TGF-beta to induce T(H)17 cells in naive Il6-/- T cells and that IL-21-receptor-deficient T cells are defective in generating a T(H)17 response. ..
  27. Karnowski A, Chevrier S, Belz G, Mount A, Emslie D, D Costa K, et al. B and T cells collaborate in antiviral responses via IL-6, IL-21, and transcriptional activator and coactivator, Oct2 and OBF-1. J Exp Med. 2012;209:2049-64 pubmed publisher
    ..Finally, the transcriptional activator Oct2 and its cofactor OBF-1 were identified as regulators of Il6 expression in B cells. ..
  28. Bessa J, Kopf M, Bachmann M. Cutting edge: IL-21 and TLR signaling regulate germinal center responses in a B cell-intrinsic manner. J Immunol. 2010;184:4615-9 pubmed publisher
    ..Hence, IL-21 acts directly on B cells and cooperates with TLR signaling for optimal B cell responses. ..
  29. Ozaki K, Kikly K, Michalovich D, Young P, Leonard W. Cloning of a type I cytokine receptor most related to the IL-2 receptor beta chain. Proc Natl Acad Sci U S A. 2000;97:11439-44 pubmed
    We have identified a type I cytokine receptor, which we have termed novel interleukin receptor (NILR), that is most related to the IL-2 receptor beta chain (IL-2Rbeta) and physically adjacent to the IL-4 receptor alpha chain gene on ..
  30. Elsaesser H, Sauer K, Brooks D. IL-21 is required to control chronic viral infection. Science. 2009;324:1569-72 pubmed publisher
    ..Thus, IL-21 specifically sustains CD8+ T cell effector activity and provides a mechanism of CD4+ T cell help during chronic viral infection...
  31. Herber D, Brown T, Liang S, Young D, Collins M, Dunussi Joannopoulos K. IL-21 has a pathogenic role in a lupus-prone mouse model and its blockade with IL-21R.Fc reduces disease progression. J Immunol. 2007;178:3822-30 pubmed
    ..From a clinical standpoint, these results suggest that blocking IL-21 in systemic lupus erythematosus patients may represent a promising novel therapeutic approach. ..
  32. Pot C, Jin H, Awasthi A, Liu S, Lai C, Madan R, et al. Cutting edge: IL-27 induces the transcription factor c-Maf, cytokine IL-21, and the costimulatory receptor ICOS that coordinately act together to promote differentiation of IL-10-producing Tr1 cells. J Immunol. 2009;183:797-801 pubmed publisher
    ..ICOS further promotes IL-27-driven Tr1 cells. Each of those elements is essential, because loss of c-Maf, IL-21-signaling, or ICOS decreases the frequency of IL-27-induced differentiation of IL-10-producing Tr1 cells. ..
  33. Peters A, Pitcher L, Sullivan J, Mitsdoerffer M, Acton S, Franz B, et al. Th17 cells induce ectopic lymphoid follicles in central nervous system tissue inflammation. Immunity. 2011;35:986-96 pubmed publisher
    ..Thus, Th17 cells are uniquely endowed to induce tissue inflammation, characterized by ectopic lymphoid follicles within the target organ. ..
  34. Hill G, Olver S, Kuns R, Varelias A, Raffelt N, Don A, et al. Stem cell mobilization with G-CSF induces type 17 differentiation and promotes scleroderma. Blood. 2010;116:819-28 pubmed publisher
    ..This study provides a logical explanation for the propensity of allogeneic stem cell transplantation to invoke sclerodermatous GVHD and suggests a therapeutic strategy for intervention. ..
  35. Collins C, Speck S. Interleukin 21 signaling in B cells is required for efficient establishment of murine gammaherpesvirus latency. PLoS Pathog. 2015;11:e1004831 pubmed publisher
  36. Sun J, Dodd H, Moser E, Sharma R, Braciale T. CD4+ T cell help and innate-derived IL-27 induce Blimp-1-dependent IL-10 production by antiviral CTLs. Nat Immunol. 2011;12:327-34 pubmed publisher
    ..These findings reveal a previously unrecognized pathway that coordinates signals derived from innate and helper T cells to control the production of a regulatory cytokine by CTLs during acute viral infection. ..
  37. McGuire H, Vogelzang A, Ma C, Hughes W, Silveira P, Tangye S, et al. A subset of interleukin-21+ chemokine receptor CCR9+ T helper cells target accessory organs of the digestive system in autoimmunity. Immunity. 2011;34:602-15 pubmed publisher
    ..Thus, CCR9+ Th cells are a subset of IL-21-producing T helper cells that influence regional specification of autoimmune diseases that affect accessory organs of the digestive system. ..
  38. Lei L, He Z, Zhao C, Sun X, Zhong X. Elevated frequencies of CD4(+) IL-21(+) T, CD4(+) IL-21R(+) T and IL-21(+) Th17 cells, and increased levels of IL-21 in bleomycin-induced mice may be associated with dermal and pulmonary inflammation and fibrosis. Int J Rheum Dis. 2016;19:392-404 pubmed publisher
    ..IL-21 may play an important role in the pathogenesis of SSc as a Th17 effector cytokine, and IL-21 may induce the differentiation of Th17 cells in the BLM-induced SSc mouse model. ..
  39. Wan C, Oh J, Li P, West E, Wong E, Andraski A, et al. The cytokines IL-21 and GM-CSF have opposing regulatory roles in the apoptosis of conventional dendritic cells. Immunity. 2013;38:514-27 pubmed publisher
    ..T cells caused more severe colitis with increased DCs and interferon-γ (IFN-γ)-producing CD4+ T cells in Il21r(-/-)Rag2(-/-) mice (which lack T cells and have IL-21-unresponsive DCs) than in Rag2(-/-) mice...
  40. Lee Y, Mitsdoerffer M, Xiao S, Gu G, Sobel R, Kuchroo V. IL-21R signaling is critical for induction of spontaneous experimental autoimmune encephalomyelitis. J Clin Invest. 2015;125:4011-20 pubmed publisher
    ..b>Il21r deletion in 2D2xTH mice reduced the incidence and severity of spontaneous EAE, which was associated with a defect ..
  41. Apetoh L, Quintana F, Pot C, Joller N, Xiao S, Kumar D, et al. The aryl hydrocarbon receptor interacts with c-Maf to promote the differentiation of type 1 regulatory T cells induced by IL-27. Nat Immunol. 2010;11:854-61 pubmed publisher
    ..Manipulating AhR signaling could therefore be beneficial in the resolution of excessive inflammatory responses...
  42. Bubier J, Sproule T, Foreman O, Spolski R, Shaffer D, Morse H, et al. A critical role for IL-21 receptor signaling in the pathogenesis of systemic lupus erythematosus in BXSB-Yaa mice. Proc Natl Acad Sci U S A. 2009;106:1518-23 pubmed publisher
    ..IL-21 arising from an abnormal population of CD4 T cells is thus central to the development of this lethal disease, and, more generally, could play an important role in human SLE and related autoimmune disorders. ..
  43. Moretto M, Khan I. IL-21 Is Important for Induction of KLRG1+ Effector CD8 T Cells during Acute Intracellular Infection. J Immunol. 2016;196:375-84 pubmed publisher
    ..To the best of our knowledge, this report demonstrates a critical role for IL-21 in the generation of a primary effector CD8 T cell response to an infectious disease model. ..
  44. Singh N, Chen C, Schwartz R. The impact of T cell intrinsic antigen adaptation on peripheral immune tolerance. PLoS Biol. 2006;4:e340 pubmed
    ..These extrinsic mechanisms prevented the effector differentiation of the autoreactive T cells and reduced their precursor frequency, in vivo. ..
  45. Sweet R, Ols M, Cullen J, Milam A, Yagita H, Shlomchik M. Facultative role for T cells in extrafollicular Toll-like receptor-dependent autoreactive B-cell responses in vivo. Proc Natl Acad Sci U S A. 2011;108:7932-7 pubmed publisher
  46. Chou C, Verbaro D, Tonc E, Holmgren M, Cella M, Colonna M, et al. The Transcription Factor AP4 Mediates Resolution of Chronic Viral Infection through Amplification of Germinal Center B Cell Responses. Immunity. 2016;45:570-582 pubmed publisher
    ..These results indicate that AP4 integrates T-cell-mediated selection and sustained expansion of GC B cells for humoral immunity. ..
  47. Wang T, Cunningham A, Dokun A, Hazarika S, HOUSTON K, Chen L, et al. Loss of interleukin-21 receptor activation in hypoxic endothelial cells impairs perfusion recovery after hindlimb ischemia. Arterioscler Thromb Vasc Biol. 2015;35:1218-25 pubmed publisher
    ..In vivo, either knockout Il21r or blocking IL-21 signaling by treating with IL-21R-Fc (fusion protein that blocks IL-21 binding to its receptor) ..
  48. Lee H, Keum S, Sheng H, Warner D, Lo D, Marchuk D. Natural allelic variation of the IL-21 receptor modulates ischemic stroke infarct volume. J Clin Invest. 2016;126:2827-38 pubmed publisher
    ..The gene encoding the IL-21 receptor (Il21r) showed a marked difference in strain-specific transcription levels and coding variants in neonatal and adult ..
  49. Liu W, Dienz O, Roberts B, Moussawi M, Rincon M, Huber S. IL-21R expression on CD8+ T cells promotes CD8+ T cell activation in coxsackievirus B3 induced myocarditis. Exp Mol Pathol. 2012;92:327-33 pubmed publisher
    ..These data demonstrate that IL-21 signaling directly in the CD8+ cell population is required for CVB3-induced myocarditis. ..
  50. Kim S, Xiang W, Kwak C, Yang Y, Lin X, Ota M, et al. GPR15-mediated homing controls immune homeostasis in the large intestine mucosa. Science. 2013;340:1456-9 pubmed publisher
    ..Our findings thus describe a T cell-homing receptor for LILP and indicate that GPR15 plays a role in mucosal immune tolerance largely by regulating the influx of Tregs. ..
  51. Simard N, Konforte D, Tran A, Esufali J, Leonard W, Paige C. Analysis of the role of IL-21 in development of murine B cell progenitors in the bone marrow. J Immunol. 2011;186:5244-53 pubmed publisher
    ..We also report in this paper that IL-21 is expressed by BM CD4(+) T cells. These results provide evidence that IL-21R is functional in B cell progenitors and indicate that IL-21 regulates B cell development. ..
  52. Lee C, Raz R, Gimeno R, Gertner R, Wistinghausen B, Takeshita K, et al. STAT3 is a negative regulator of granulopoiesis but is not required for G-CSF-dependent differentiation. Immunity. 2002;17:63-72 pubmed
  53. Søndergaard H, Coquet J, Uldrich A, McLaughlin N, Godfrey D, Sivakumar P, et al. Endogenous IL-21 restricts CD8+ T cell expansion and is not required for tumor immunity. J Immunol. 2009;183:7326-36 pubmed publisher
  54. McPhee C, Bubier J, Sproule T, Park G, Steinbuck M, Schott W, et al. IL-21 is a double-edged sword in the systemic lupus erythematosus-like disease of BXSB.Yaa mice. J Immunol. 2013;191:4581-8 pubmed publisher
    ..These results indicate that IL-21 has both disease-promoting and disease-suppressive effects in the autoimmune disease of BXSB.Yaa mice. ..
  55. Sutherland A, Joller N, Michaud M, Liu S, Kuchroo V, Grusby M. IL-21 promotes CD8+ CTL activity via the transcription factor T-bet. J Immunol. 2013;190:3977-84 pubmed publisher
    ..Thus, IL-21 drives CD8(+) CTL differentiation via the actions of the transcription factor T-bet. ..
  56. Mascanfroni I, Yeste A, Vieira S, Burns E, Patel B, Sloma I, et al. IL-27 acts on DCs to suppress the T cell response and autoimmunity by inducing expression of the immunoregulatory molecule CD39. Nat Immunol. 2013;14:1054-63 pubmed publisher
    ..Finally, therapeutic vaccination with IL-27-conditioned DCs suppressed established relapsing-remitting EAE. Thus, IL-27 signaling in DCs limited pathogenic T cell responses and the development of autoimmunity. ..
  57. Yi J, Ingram J, Zajac A. IL-21 deficiency influences CD8 T cell quality and recall responses following an acute viral infection. J Immunol. 2010;185:4835-45 pubmed publisher
    ..Collectively, these studies highlight the potential roles of IL-21 in determining the quality of CD8 T cell responses postinfection...
  58. Marnik E, Wang X, Sproule T, Park G, Christianson G, Lane Reticker S, et al. Precocious Interleukin 21 Expression in Naive Mice Identifies a Natural Helper Cell Population in Autoimmune Disease. Cell Rep. 2017;21:208-221 pubmed publisher
    ..These studies link IL-21 to T cell ontogeny, self-reactivity, and humoral autoimmunity. ..
  59. Attridge K, Kenefeck R, Wardzinski L, Qureshi O, Wang C, Manzotti C, et al. IL-21 promotes CD4 T cell responses by phosphatidylinositol 3-kinase-dependent upregulation of CD86 on B cells. J Immunol. 2014;192:2195-201 pubmed publisher
    ..These data pinpoint CD86 upregulation as an additional mechanism by which IL-21 can elicit immunomodulatory effects. ..
  60. Coquet J, Schuijs M, Smyth M, Deswarte K, Beyaert R, Braun H, et al. Interleukin-21-Producing CD4(+) T Cells Promote Type 2 Immunity to House Dust Mites. Immunity. 2015;43:318-30 pubmed publisher
    ..b>Il21r(-/-) mice developed reduced type 2 responses and the IL-21 receptor (IL-21R) enhanced Th2 cell function in a cell-..
  61. Bunting M, Varelias A, Souza Fonseca Guimaraes F, Schuster I, Lineburg K, Kuns R, et al. GVHD prevents NK-cell-dependent leukemia and virus-specific innate immunity. Blood. 2017;129:630-642 pubmed publisher
    ..Thus, during GVHD, donor T cells compete with NK cells for IL-15 thereby inducing profound defects in NK-cell reconstitution that compromise both leukemia and pathogen-specific immunity. ..
  62. Van Belle T, Nierkens S, Arens R, Von Herrath M. Interleukin-21 receptor-mediated signals control autoreactive T cell infiltration in pancreatic islets. Immunity. 2012;36:1060-72 pubmed publisher
    ..antigen, major histocompatibility complex (MHC) class II, and CD86 was provided to autoreactive effector cells in Il21r(-/-) mice, impairing CD4(+) T cell activation, CD40:CD40L interactions, and pancreatic infiltration by ..
  63. Liu L, Xu Y, Wang J, Li H. Upregulated IL-21 and IL-21 receptor expression is involved in experimental autoimmune uveitis (EAU). Mol Vis. 2009;15:2938-44 pubmed
    ..The findings revealed that increased IL-21 and IL-21R expression may be involved in the development of EAU, possibly by promoting IL-17 secretion. ..
  64. Mittal D, Caramia F, Michiels S, Joensuu H, Kellokumpu Lehtinen P, Sotiriou C, et al. Improved Treatment of Breast Cancer with Anti-HER2 Therapy Requires Interleukin-21 Signaling in CD8+ T Cells. Cancer Res. 2016;76:264-74 pubmed publisher
    ..of trastuzumab benefit on distant disease-free survival was higher for increasing expression of the IL21 receptor (IL21R). Therefore, we investigated a possible role for IL21 signaling in promoting HER2 mAb therapeutic efficacy...
  65. Yoshizaki A, Miyagaki T, DiLillo D, Matsushita T, Horikawa M, Kountikov E, et al. Regulatory B cells control T-cell autoimmunity through IL-21-dependent cognate interactions. Nature. 2012;491:264-8 pubmed publisher
    ..The ex vivo expansion and reinfusion of autologous B10 cells may provide a novel and effective in vivo treatment for severe autoimmune diseases that are resistant to current therapies. ..
  66. Spolski R, Wang L, Wan C, Bonville C, Domachowske J, Kim H, et al. IL-21 promotes the pathologic immune response to pneumovirus infection. J Immunol. 2012;188:1924-32 pubmed publisher
    ..We found that PVM-infected mice expressed IL-21 in lung CD4(+) T cells. Following infection, Il21r(-/-) mice exhibited less lung infiltration by neutrophils than did wild-type (WT) mice and correspondingly had ..
  67. Bubier J, Bennett S, Sproule T, Lyons B, Olland S, Young D, et al. Treatment of BXSB-Yaa mice with IL-21R-Fc fusion protein minimally attenuates systemic lupus erythematosus. Ann N Y Acad Sci. 2007;1110:590-601 pubmed
    ..This experiment provides preliminary evidence for a role of IL-21 in modulating the severity of SLE in BXSB-Yaa mice. ..
  68. Rankin A, Guay H, Herber D, Bertino S, Duzanski T, Carrier Y, et al. IL-21 receptor is required for the systemic accumulation of activated B and T lymphocytes in MRL/MpJ-Fas(lpr/lpr)/J mice. J Immunol. 2012;188:1656-67 pubmed publisher
    ..Together, our data highlighted the novel observation that IL-21 is a critical regulator of multiple pathogenic B and T cell effector subsets in MRL(lpr) mice. ..