Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

IL-21 acts as a promising therapeutic target in systemic lupus erythematosus by regulating plasma cell differentiation

Cellular & Molecular Immunology volume 12, pages 31–39 (2015)Cite this article

Abstract

Plasma cells, which secrete auto-antibodies, are considered to be the arch-criminal of autoimmune diseases such as systemic lupus erythematosus, but there are many cytokines involved in inducing the differentiation of B-cell subsets into plasma cells. Here, we emphasize IL-21, which has emerged as the most potent inducer of plasma cell differentiation. In this review, we focused on the promoting effects of IL-21 on plasma cell differentiation and discuss how these effects contribute to B cell-mediated autoimmune disease.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Hostmann A, Jacobi A, Mei H, Hiepe F, Dörner T . Peripheral B cell abnormalities and disease activity in systemic lupus erythematosus. Lupus 2008; 17: 1064–1069.

    CAS  PubMed  Google Scholar 

  2. Mariño E, Grey ST . B cells as effectors and regulators of autoimmunity. Autoimmunity 2012; 45: 377–387.

    PubMed  Google Scholar 

  3. Liu R, Wu Q, Su D, Che N, Chen H, Geng L et al. A regulatory effect of IL-21 on T follicular helper-like cell and B cell in rheumatoid arthritis. Arthritis Res Ther 2012; 14: R255.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Nakou M, Papadimitraki E, Fanouriakis A, Bertsias G, Choulaki C, Goulidaki N et al. Interleukin-21 is increased in active systemic lupus erythematosus patients and contributes to generation of plasma B cells. Clin Exp Rheumatol 2012; 31: 172–179.

    PubMed  Google Scholar 

  5. Terrier B, Costedoat-Chalumeau N, Garrido M, Geri G, Rosenzwajg M, Musset L et al. Interleukin 21 correlates with T cell and B cell subset alterations in systemic lupus erythematosus. J Rheumatol 2012; 39: 1819–1828.

    CAS  PubMed  Google Scholar 

  6. Bubier JA, Sproule TJ, Foreman O, Spolski R, Shaffer DJ, Morse HC 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 USA 2009; 106: 1518–1523.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Simard N, Konforte D, Tran AH, Esufali J, Leonard WJ, Paige CJ . Analysis of the role of IL-21 in development of murine B cell progenitors in the bone marrow. J Immunol 2011; 186: 5244–5253.

    CAS  PubMed  Google Scholar 

  8. Pieper K, Grimbacher B, Eibel H . B-cell biology and development. J Allergy Clin Immunol 2013; 131: 959–971.

    CAS  PubMed  Google Scholar 

  9. Tedder TF . CD19: a promising B cell target for rheumatoid arthritis. Nat Rev Rheumatol 2009; 5: 572–577.

    CAS  PubMed  Google Scholar 

  10. Lipsky PE . Systemic lupus erythematosus: an autoimmune disease of B cell hyperactivity. Nat Immunol 2001; 2: 764–766.

    CAS  PubMed  Google Scholar 

  11. Lopes-Carvalho T, Kearney JF . Development and selection of marginal zone B cells. Immunol Rev 2004; 197: 192–205.

    PubMed  Google Scholar 

  12. Shapiro-Shelef M, Calame K . Regulation of plasma-cell development. Nat Rev Immunol 2005; 5: 230–242.

    CAS  PubMed  Google Scholar 

  13. Martin F, Oliver AM, Kearney JF . Marginal zone and B1 B cells unite in the early response against T-independent blood-borne particulate antigens. Immunity 2001; 14: 617–629.

    CAS  PubMed  Google Scholar 

  14. Liu Z, Zou Y, Davidson A . Plasma cells in systemic lupus erythematosus: the long and short of it all. Eur J Immunol 2011; 41: 588–591.

    CAS  PubMed  Google Scholar 

  15. Ma CS, Deenick EK, Batten M, Tangye SG . The origins, function, and regulation of T follicular helper cells. J Exp Med 2012; 209: 1241–1253.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Oracki SA, Walker JA, Hibbs ML, Corcoran LM, Tarlinton DM . Plasma cell development and survival. Immunol Rev 2010; 237: 140–159.

    CAS  PubMed  Google Scholar 

  17. Paus D, Phan TG, Chan TD, Gardam S, Basten A, Brink R . Antigen recognition strength regulates the choice between extrafollicular plasma cell and germinal center B cell differentiation. J Exp Med 2006; 203: 1081–1091.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Lee SK, Rigby RJ, Zotos D, Tsai LM, Kawamoto S, Marshall JL et al. B cell priming for extrafollicular antibody responses requires Bcl-6 expression by T cells. J Exp Med 2011; 208: 1377–1388.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Nikbakht N, Shen S, Manser T . Cutting edge: macrophages are required for localization of antigen-activated B cells to the follicular perimeter and the subsequent germinal center response. J Immunol 2013; 190: 4923–4927.

    CAS  PubMed  Google Scholar 

  20. Vinuesa CG, Sanz I, Cook MC . Dysregulation of germinal centres in autoimmune disease. Nat Rev Immunol 2009; 9: 845–857.

    CAS  PubMed  Google Scholar 

  21. Luther SA . Plasma cell precursors: long-distance travelers looking for a home. Immunity 2010; 33: 9–11.

    CAS  PubMed  Google Scholar 

  22. Bortnick A, Allman D . What is and what should always have been: long-lived plasma cells induced by T cell-independent antigens. J Immunol 2013; 190: 5913–5918.

    CAS  PubMed  Google Scholar 

  23. Hoyer BF, Moser K, Hauser AE, Peddinghaus A, Voigt C, Eilat D et al. Short-lived plasmablasts and long-lived plasma cells contribute to chronic humoral autoimmunity in NZB/W mice. Arthritis Res Ther 2004; 6: 9.

    PubMed Central  Google Scholar 

  24. Kemeny DM . The role of the T follicular helper cells in allergic disease. Cell Mol Immunol 2012; 9: 386–389.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Shekhar S, Yang X . The darker side of follicular helper T cells: from autoimmunity to immunodeficiency. Cell Mol Immunol 2012; 9: 380–385.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Rodríguez-Bayona B, Ramos-Amaya A, Bernal J, Campos-Caro A, Brieva JA . Cutting edge: IL-21 derived from human follicular helper T cells acts as a survival factor for secondary lymphoid organ, but not for bone marrow, plasma cells. J Immunol 2012; 188: 1578–1581.

    PubMed  Google Scholar 

  27. Jeannin P, Lecoanet S, Delneste Y, Gauchat JF, Bonnefoy JY . IgE versus IgG4 production can be differentially regulated by IL-10. J Immunol 1998; 160: 3555–3561.

    CAS  PubMed  Google Scholar 

  28. Pene J, Gauchat JF, Lecart S, Drouet E, Guglielmi P, Boulay V et al. Cutting edge: IL-21 is a switch factor for the production of IgG1 and IgG3 by human B cells. J Immunol 2004; 172: 5154–5157.

    CAS  PubMed  Google Scholar 

  29. Pratama A, Vinuesa CG . Control of TFH cell numbers: why and how? Immunol Cell Biol 2014; 92: 40–48.

    CAS  PubMed  Google Scholar 

  30. Yu D, Linterman M . The temporospatial control of Tfh cells. Immunol Cell Biol 2014; 92: 20–21.

    CAS  PubMed  Google Scholar 

  31. Vogelzang A, McGuire HM, Yu D, Sprent J, Mackay CR, King C . A fundamental role for interleukin-21 in the generation of T follicular helper cells. Immunity 2008; 29: 127–137.

    CAS  PubMed  Google Scholar 

  32. Zotos D, Coquet JM, 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: 365–378.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Ettinger R, Kuchen S, Lipsky PE . The role of IL-21 in regulating B-cell function in health and disease. Immunol Rev 2008; 223: 60–86.

    CAS  PubMed  Google Scholar 

  34. Todd DJ, Lee AH, Glimcher LH . The endoplasmic reticulum stress response in immunity and autoimmunity. Nat Rev Immunol 2008; 8: 663–674.

    CAS  PubMed  Google Scholar 

  35. Crotty S, Johnston RJ, Schoenberger SP . Effectors and memories: Bcl-6 and Blimp-1 in T and B lymphocyte differentiation. Nat Immunol 2010; 11: 114–120.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Ochiai K, Muto A, Tanaka H, Takahashi S, Igarashi K . Regulation of the plasma cell transcription factor Blimp-1 gene by Bach2 and Bcl6. Int Immunol 2008; 20: 453–460.

    CAS  PubMed  Google Scholar 

  37. Angelin-Duclos C, Cattoretti G, Lin KI, Calame K . Commitment of B lymphocytes to a plasma cell fate is associated with Blimp-1 expression in vivo. J Immunol 2000; 165: 5462–5471.

    CAS  PubMed  Google Scholar 

  38. Johnston RJ, Poholek AC, DiToro D, Yusuf I, Eto D, Barnett B et al. Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation. Science 2009; 325: 1006–1010.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Nurieva RI, Chung Y, Martinez GJ, Yang XO, Tanaka S, Matskevitch TD et al. Bcl6 mediates the development of T follicular helper cells. Science 2009; 325: 1001–1005.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Parrish-Novak J, Dillon SR, Nelson A, Hammond A, Sprecher C, Gross JA et al. Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Nature 2000; 408: 57–63.

    CAS  PubMed  Google Scholar 

  41. Wurster AL, Rodgers VL, Satoskar AR, Whitters MJ, Young DA, Collins M et al. Interleukin 21 is a T helper (Th) cell 2 cytokine that specifically inhibits the differentiation of naive Th cells into interferon-producing Th1 cells. J Exp Med 2002; 196: 969–977.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Fantini MC, Rizzo A, Fina D, Caruso R, Becker C, Neurath MF et al. IL-21 regulates experimental colitis by modulating the balance between Treg and Th17 cells. Eur J Immunol 2007; 37: 3155–3163.

    CAS  PubMed  Google Scholar 

  43. Korn T, Bettelli E, Gao W, Awasthi A, Jager A, Strom TB et al. IL-21 initiates an alternative pathway to induce proinflammatory TH17 cells. Nature 2007; 448: 484–487.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Nurieva R, Yang XO, Martinez G, Zhang Y, Panopoulos AD, Ma L et al. Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 2007; 448: 480–483.

    CAS  PubMed  Google Scholar 

  45. Zhou L, Ivanov II, Spolski R, Min R, Shenderov K, Egawa T et al. IL-6 programs TH-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol 2007; 8: 967–974.

    CAS  PubMed  Google Scholar 

  46. 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: 1369–1379.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. King C, Tangye SG, Mackay CR . T follicular helper (TFH) cells in normal and dysregulated immune responses. Annu Rev Immunol 2008; 26: 741–766.

    CAS  PubMed  Google Scholar 

  48. Odegard JM, Marks BR, DiPlacido LD, Poholek AC, Kono DH, Dong C et al. ICOS-dependent extrafollicular helper T cells elicit IgG production via IL-21 in systemic autoimmunity. J Exp Med 2008; 205: 2873–2886.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Kasaian MT, Whitters MJ, Carter LL, Lowe LD, Jussif JM, 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: 559–569.

    CAS  PubMed  Google Scholar 

  50. Ozaki K, Spolski R, Feng CG, Qi CF, Cheng J, Sher A et al. A critical role for IL-21 in regulating immunoglobulin production. Science 2002; 298: 1630–1634.

    CAS  PubMed  Google Scholar 

  51. Herber D, Brown TP, Liang S, Young DA, 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: 3822–3830.

    CAS  PubMed  Google Scholar 

  52. Ettinger R, Sims GP, Fairhurst AM, Robbins R, da Silva YS, Spolski R et al. IL-21 induces differentiation of human naive and memory B cells into antibody-secreting plasma cells. J Immunol 2005; 175: 7867–7879.

    CAS  PubMed  Google Scholar 

  53. Pène J, Gauchat JF, Lécart S, Drouet E, Guglielmi P, Boulay V et al. Cutting edge: IL-21 is a switch factor for the production of IgG1 and IgG3 by human B cells. J Immunol 2004; 172: 5154–5157.

    PubMed  Google Scholar 

  54. Yoon SO, Zhang X, Berner P, Choi YS . IL-21 and IL-10 have redundant roles but differential capacities at different stages of plasma cell generation from human germinal center B cells. J Leukoc Biol 2009; 86: 1311–1318.

    CAS  PubMed  Google Scholar 

  55. Linterman MA, Beaton L, Yu D, Ramiscal RR, Srivastava M, Hogan JJ et al. IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center responses. J Exp Med 2010; 207: 353–363.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Hsu HC, Yang P, Wang J, Wu Q, Myers R, Chen J et al. Interleukin 17–producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice. Nat Immunol 2007; 9: 166–175.

    PubMed  Google Scholar 

  57. Luzina IG, Atamas SP, Storrer CE, Kelsoe G, Papadimitriou JC, Handwerger BS . Spontaneous formation of germinal centers in autoimmune mice. J Leukoc Biol 2001; 70: 578–584.

    CAS  PubMed  Google Scholar 

  58. Zhang X, Ing S, Fraser A, Chen M, Khan O, Zakem J et al. Follicular helper T cells: new insights into mechanisms of autoimmune diseases. Ochsner J 2013; 13: 131–139.

    PubMed  PubMed Central  Google Scholar 

  59. Lüthje K, Kallies A, Shimohakamada Y, Belz GT, Light A, Tarlinton DM et al. The development and fate of follicular helper T cells defined by an IL-21 reporter mouse. Nat Immunol 2012; 13: 491–498.

    PubMed  Google Scholar 

  60. Craft JE . Follicular helper T cells in immunity and systemic autoimmunity. Nat Rev Rheumatol 2012; 8: 337–347.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Vinuesa CG, Sanz I, Cook MC . Dysregulation of germinal centres in autoimmune disease. Nat Rev Immunol 2009; 9: 845–857.

    CAS  PubMed  Google Scholar 

  62. Block KE, Huang H . The cellular source and target of IL-21 in K/BxN autoimmune arthritis. J Immunol 2013; 191: 2948–2955.

    CAS  PubMed  Google Scholar 

  63. Kuchen S, Robbins R, Sims GP, Sheng C, Phillips TM, Lipsky PE et al. Essential role of IL-21 in B cell activation, expansion, and plasma cell generation during CD4+ T cell–B cell collaboration. J Immunol 2007; 179: 5886–5896.

    CAS  PubMed  Google Scholar 

  64. Leonard WJ, Spolski R . Interleukin-21: a modulator of lymphoid proliferation, apoptosis and differentiation. Nat Rev Immunol 2005; 5: 688–698.

    CAS  PubMed  Google Scholar 

  65. Spolski R, Leonard WJ . Interleukin-21: basic biology and implications for cancer and autoimmunity. Annu Rev Immunol 2008; 26: 57–79.

    CAS  PubMed  Google Scholar 

  66. Scheeren FA, Naspetti M, Diehl S, Schotte R, Nagasawa M, Wijnands E et al. STAT5 regulates the self-renewal capacity and differentiation of human memory B cells and controls Bcl-6 expression. Nat Immunol 2005; 6: 303–313.

    CAS  PubMed  Google Scholar 

  67. Reljic R, Wagner SD, Peakman LJ, Fearon DT . Suppression of signal transducer and activator of transcription 3-dependent B lymphocyte terminal differentiation by BCL-6. J Exp Med 2000; 192: 1841–1848.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Arguni E, Arima M, Tsuruoka N, Sakamoto A, Hatano M, Tokuhisa T . JunD/AP-1 and STAT3 are the major enhancer molecules for high Bcl6 expression in germinal center B cells. Int Immunol 2006; 18: 1079–1089.

    CAS  PubMed  Google Scholar 

  69. Ozaki K, Spolski R, Ettinger R, Kim HP, Wang G, Qi CF et al. Regulation of B cell differentiation and plasma cell generation by IL-21, a novel inducer of Blimp-1 and Bcl-6. J Immunol 2004; 173: 5361–5371.

    CAS  PubMed  Google Scholar 

  70. Rodríguez-Bayona B, Ramos-Amaya A, López-Blanco R, Campos-Caro A, Brieva JA . STAT-3 activation by differential cytokines is critical for human in vivo-generated plasma cell survival and Ig secretion. J Immunol 2013; 191: 4996–5004.

    PubMed  Google Scholar 

  71. Strengell M, Matikainen S, Sirén J, Lehtonen A, Foster D, Julkunen I et al. IL-21 in synergy with IL-15 or IL-18 enhances IFN-γ production in human NK and T cells. J Immunol 2003; 170: 5464–5469.

    CAS  PubMed  Google Scholar 

  72. Zeng R, Spolski R, Casas E, Zhu W, Levy DE, Leonard WJ . The molecular basis of IL-21-mediated proliferation. Blood 2007; 109: 4135–4142.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Ding BB, Bi E, Chen H, Yu JJ, Ye BH . IL-21 and CD40 L synergistically promote plasma cell differentiation through upregulation of Blimp-1 in human B Cells. J Immunol 2013; 190: 1827–1836.

    CAS  PubMed  Google Scholar 

  74. Basso K, Dalla-Favera R . Roles of BCL6 in normal and transformed germinal center B cells. Immunol Rev 2012; 247: 172–183.

    PubMed  Google Scholar 

  75. Shapiro-Shelef M, Calame K . Regulation of plasma-cell development. Nat Rev Immunol 2005; 5: 230–242.

    CAS  PubMed  Google Scholar 

  76. Zhou Z, Ren Y, Hu Z . Blimp-1 siRNA inhibits B cell differentiation and prevents the development of lupus in mice. Hum Immunol 2012; 74: 297–301.

    PubMed  Google Scholar 

  77. Shaffer A, Yu X, He Y, Boldrick J, Chan EP, Staudt LM . BCL-6 represses genes that function in lymphocyte differentiation, inflammation, and cell cycle control. Immunity 2000; 13: 199–212.

    CAS  PubMed  Google Scholar 

  78. Diehl SA, Schmidlin H, Nagasawa M, van Haren SD, Kwakkenbos MJ, Yasuda E et al. STAT3-mediated up-regulation of BLIMP1 is coordinated with BCL6 down-regulation to control human plasma cell differentiation. J Immunol 2008; 180: 4805–4815.

    CAS  PubMed  Google Scholar 

  79. Martins G, Calame K . Regulation and functions of Blimp-1 in T and B lymphocytes. Annu Rev Immunol 2008; 26: 133–169.

    CAS  PubMed  Google Scholar 

  80. Zhu J, Paul WE . CD4 T cells: fates, functions, and faults. Blood 2008; 112: 1557–1569.

    CAS  PubMed  PubMed Central  Google Scholar 

  81. King C, Tangye SG, Mackay CR . T follicular helper (TFH) cells in normal and dysregulated immune responses. Annu Rev Immunol 2008; 26: 741–766.

    CAS  PubMed  Google Scholar 

  82. Ma CS, Suryani S, Avery DT, Chan A, Nanan R, Santner-Nanan B et al. Early commitment of naive human CD4+ T cells to the T follicular helper (TFH) cell lineage is induced by IL-12. Immunol Cell Biol 2009; 87: 590–600.

    CAS  PubMed  Google Scholar 

  83. Fazilleau N, McHeyzer-Williams LJ, Rosen H, McHeyzer-Williams MG . The function of follicular helper T cells is regulated by the strength of T cell antigen receptor binding. Nat Immunol 2009; 10: 375–384.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Pelletier N, McHeyzer-Williams LJ, Wong KA, Urich E, Fazilleau N, McHeyzer-Williams MG . Plasma cells negatively regulate the follicular helper T cell program. Nat Immunol 2010; 11: 1110–1118.

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Chtanova T, Tangye SG, Newton R, Frank N, Hodge MR, Rolph MS et al. T follicular helper cells express a distinctive transcriptional profile, reflecting their role as non-Th1/Th2 effector cells that provide help for B cells. J Immunol 2004; 173: 68–78.

    CAS  PubMed  Google Scholar 

  86. Nurieva R, Yang XO, Martinez G, Zhang Y, Panopoulos AD, Ma L et al. Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 2007; 448: 480–483.

    CAS  PubMed  Google Scholar 

  87. Sawalha AH, Kaufman KM, Kelly JA, Adler AJ, Aberle T, Kilpatrick J et al. Genetic association of interleukin-21 polymorphisms with systemic lupus erythematosus. Ann Rheum Dis 2008; 67: 458–461.

    CAS  PubMed  Google Scholar 

  88. Webb R, Merrill JT, Kelly JA, Sestak A, Kaufman KM, Langefeld CD et al. A polymorphism within IL21R confers risk for systemic lupus erythematosus. Arthritis Rheum 2009; 60: 2402–2407.

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Biswas PS, Kang K, Gupta S, Bhagat G, Pernis AB . A murine autoimmune model of rheumatoid arthritis and systemic lupus erythematosus associated with deregulated production of IL-17 and IL-21. Methods Mol Biol 2012; 900: 233–251.

    CAS  PubMed  Google Scholar 

  90. Vinuesa CG, Cook MC, Angelucci C, Athanasopoulos V, Rui L, Hill KM et al. A RING-type ubiquitin ligase family member required to repress follicular helper T cells and autoimmunity. Nature 2005; 435: 452–458.

    CAS  PubMed  Google Scholar 

  91. Herber D, Brown TP, Liang S, Young DA, 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: 3822–3830.

    CAS  PubMed  Google Scholar 

  92. Luo J, Niu X, Liu H, Zhang M, Chen M, Deng S . Up-regulation of transcription factor Blimp1 in systemic lupus erythematosus. Mol Immunol 2013; 56: 574–582.

    CAS  PubMed  Google Scholar 

  93. McPhee CG, Bubier JA, Sproule TJ, Park G, Steinbuck MP, Schott WH et al. IL-21 is a double-edged sword in the systemic lupus erythematosus-like disease of BXSB.Yaa mice. J Immunol 2013; 191: 4581–4588.

    CAS  PubMed  Google Scholar 

  94. Rankin AL, Guay H, Herber D, Bertino SA, Duzanski TA, 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: 1656–1667.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was financially supported by the National Nature Science Foundation of China (No. 81173075, 81330081), the Specialized Research Fund for the Doctoral Program of Higher Education, China (No. 20123420110003) and the Anhui Province Nature Science Foundation for the University (No. KJ2011A177).

Author information

Authors and Affiliations

  1. Institute of Clinical Pharmacology of Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei, China

    Xiao-Mei Deng, Shang-Xue Yan & Wei Wei

Authors
  1. Xiao-Mei Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shang-Xue Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wei Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wei Wei.

Ethics declarations

Competing interests

The authors declare that there are no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Deng, XM., Yan, SX. & Wei, W. IL-21 acts as a promising therapeutic target in systemic lupus erythematosus by regulating plasma cell differentiation. Cell Mol Immunol 12, 31–39 (2015). https://doi.org/10.1038/cmi.2014.58

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/cmi.2014.58

Keywords

This article is cited by

Search

Advanced search

Quick links