Skip to main content

Advertisement

Log in

Role of interleukin-10 and interleukin-10 receptor in systemic lupus erythematosus

  • Review Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by excessive production of a variety of autoantibodies, accumulation of immune complexes, and multiple organ systems involvement. Interleukin-10 (IL-10) has an important role in the growth, survival, differentiation, and function of B cells. Abnormally increased IL-10 synthesis seems contributing to the spontaneous hyperactivity of the B cell compartment, so that it can directly result in autoantibody production by committed plasma cells, circulating immune complexes formation, and eventually in tissue and organ damage, suggesting it might associate with the development of SLE. A better understanding of the regulation of IL-10 and its receptors (IL-10R) can likely provide more valuable clues to the pathogenic mechanisms underlying specific forms of SLE, so as to pave the way toward more effective therapeutics.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Reference

  1. Ouyang W, Rutz S, Crellin NK, Valdez PA, Hymowitz SG (2011) Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu Rev Immunol 29:71–109

    Article  PubMed  CAS  Google Scholar 

  2. Fiorentino DF, Bond MW, Mosmann TR (1989) Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med 170(6):2081–2095

    Article  PubMed  CAS  Google Scholar 

  3. Wolk K, Kunz S, Asadullah K, Sabat R (2002) Cutting edge: immune cells as sources and targets of the IL-10 family members? J Immunol 168(11):5397–5402

    PubMed  CAS  Google Scholar 

  4. Murai M, Turovskaya O, Kim G, Madan R, Karp CL, Cheroutre H et al (2009) Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis. Nat Immunol 10(11):1178–1184

    Article  PubMed  CAS  Google Scholar 

  5. Roers A, Siewe L, Strittmatter E, Deckert M, Schlüter D, Stenzel W et al (2004) T cell-specific inactivation of the interleukin 10 gene in mice results in enhanced T cell responses but normal innate responses to lipopolysaccharide or skin irritation. J Exp Med 200(10):1289–1297

    Article  PubMed  CAS  Google Scholar 

  6. Blanco P, Palucka AK, Pascual V, Banchereau J (2008) Dendritic cells and cytokines in human inflammatory and autoimmune diseases. Cytokine Growth Factor Rev 19(1):41–52

    Article  PubMed  CAS  Google Scholar 

  7. Chomarat P, Rissoan MC, Banchereau J, Miossec P (1993) Interferon gamma inhibits interleukin 10 production by monocytes. J Exp Med 177(2):523–527

    Article  PubMed  CAS  Google Scholar 

  8. Fillatreau S, Sweenie CH, McGeachy MJ, Gray D, Anderton SM (2002) B cells regulate autoimmunity by provision of IL-10. Nat Immunol 3(10):944–950

    Article  PubMed  CAS  Google Scholar 

  9. Grant LR, Yao ZJ, Hedrich CM, Wang F, Moorthy A, Wilson K et al (2008) Stat4-dependent, T-bet-independent regulation of IL-10 in NK cells. Genes Immun 9(4):316–327

    Article  PubMed  CAS  Google Scholar 

  10. Mehrotra PT, Donnelly RP, Wong S, Kanegane H, Geremew A, Mostowski HS et al (1998) Production of IL-10 by human natural killer cells stimulated with IL-2 and/or IL-12. J Immunol 160(6):2637–2644

    PubMed  CAS  Google Scholar 

  11. Speiran K, Bailey DP, Fernando J, Macey M, Barnstein B, Kolawole M et al (2009) Endogenous suppression of mast cell development and survival by IL-4 and IL-10. J Leukoc Biol 85(5):826–836

    Article  PubMed  CAS  Google Scholar 

  12. Tan JC, Indelicato S, Narula SK, Zavodny PJ, Chou CC (1993) Characterization of interleukin-10 receptors on human and mouse cells. J Biol Chem 268(28):21053–21059

    PubMed  CAS  Google Scholar 

  13. Windsor WT, Syto R, Tsarbopoulos A, Zhang R, Durkin J, Baldwin S et al (1993) Disulfide bond assignments and secondary structure analysis of human and murine interleukin 10. Biochemistry 32(34):8807–8815

    Article  PubMed  CAS  Google Scholar 

  14. Walter MR, Nagabhushan TL (1995) Crystal structure of interleukin 10 reveals an interferon gamma-like fold. Biochemistry 34(38):12118–12125

    Article  PubMed  CAS  Google Scholar 

  15. Zdanov A, Schalk-Hihi C, Wlodawer A (1996) Crystal of human interleukin-10 at 1.6 A resolution and a model of a complex with its soluble receptor. Protein Sci 5(10):1955–1962

    Article  PubMed  CAS  Google Scholar 

  16. Syto R, Murgolo NJ, Braswell EH, Mui P, Huang E, Windsor WT (1998) Structural and biological stability of the human interleukin 10 homodimer. Biochemistry 37(48):16943–16951

    Article  PubMed  CAS  Google Scholar 

  17. Walter MR, Windsor WT, Nagabhushan TL, Lundell DJ, Lunn CA, Zavodny PJ et al (1995) Crystal structure of a complex between interferon-gamma and its soluble high affinity receptor. Nature 376(6537):230–235

    Article  PubMed  CAS  Google Scholar 

  18. Moore KW, de Waal MR, Coffman RL, O’Garra A (2001) Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19:683–765

    Article  PubMed  CAS  Google Scholar 

  19. Moore KW, O’Garra A, de Waal MR, Vieira P, Mosmann TR (1993) Interleukin-10. Annu Rev Immunol 11:165–190

    Article  PubMed  CAS  Google Scholar 

  20. Akdis CA, Blaser K (2001) Mechanisms of interleukin-10-mediated immune suppression. Immunology 103(2):131–136

    Article  PubMed  CAS  Google Scholar 

  21. Schall TJ, Bacon K, Toy KJ, Goeddel DV (1990) Selective attraction of monocytes and T lymphocytes of the memory phenotype by cytokine RANTES. Nature 347(6294):669–671

    Article  PubMed  CAS  Google Scholar 

  22. Cai G, Kastelein RA, Hunter CA (1999) IL-10 enhances NK cell proliferation, cytotoxicity and production of IFN-gamma when combined with IL-18. Eur J Immunol 29(9):2658–2665

    Article  PubMed  CAS  Google Scholar 

  23. Donnelly RP, Dickensheets H, Finbloom DS (1999) The interleukin-10 signal transduction pathway and regulation of gene expression in mononuclear phagocytes. J Interferon Cytokine Res 19(6):563–573

    Article  PubMed  CAS  Google Scholar 

  24. Kotenko SV, Pestka S (2000) Jak-Stat signal transduction pathway through the eyes of cytokine class II receptor complexes. Oncogene 19(21):2557–2565

    Article  PubMed  CAS  Google Scholar 

  25. Logsdon NJ, Jones BC, Josephson K, Cook J, Walter MR (2002) Comparison of interleukin-22 and interleukin-10 soluble receptor complexes. J Interferon Cytokine Res 22(11):1099–1112

    Article  PubMed  CAS  Google Scholar 

  26. Ding Y, Qin L, Zamarin D, Kotenko SV, Pestka S, Moore KW et al (2001) Differential IL-10R1 expression plays a critical role in IL-10-mediated immune regulation. J Immunol 167(12):6884–6892

    PubMed  CAS  Google Scholar 

  27. Kunz S, Wolk K, Witte E, Witte K, Doecke WD, Volk HD et al (2006) Interleukin (IL)-19, IL-20 and IL-24 are produced by and act on keratinocytes and are distinct from classical ILs. Exp Dermatol 15(12):991–1004

    Article  PubMed  CAS  Google Scholar 

  28. Wolk K, Witte E, Reineke U, Witte K, Friedrich M, Sterry W et al (2005) Is there an interaction between interleukin-10 and interleukin-22? Genes Immun 6(1):8–18

    PubMed  CAS  Google Scholar 

  29. Reineke U, Schneider-Mergener J, Glaser RW, Stigler RD, Seifert M, Volk HD et al (1999) Evidence for conformationally different states of interleukin-10: binding of a neutralizing antibody enhances accessibility of a hidden epitope. J Mol Recognit 12(4):242–248

    Article  PubMed  CAS  Google Scholar 

  30. Yoon SI, Logsdon NJ, Sheikh F, Donnelly RP, Walter MR (2006) Conformational changes mediate interleukin-10 receptor 2 (IL-10R2) binding to IL-10 and assembly of the signaling complex. J Biol Chem 281(46):35088–35096

    Article  PubMed  CAS  Google Scholar 

  31. Weber-Nordt RM, Riley JK, Greenlund AC, Moore KW, Darnell JE, Schreiber RD (1996) Stat3 recruitment by two distinct ligand-induced, tyrosine-phosphorylated docking sites in the interleukin-10 receptor intracellular domain. J Biol Chem 271(44):27954–27961

    Article  PubMed  CAS  Google Scholar 

  32. Dummer W, Bastian BC, Ernst N, Schänzle C, Schwaaf A, Bröcker EB (1996) Interleukin-10 production in malignant melanoma: preferential detection of IL-10-secreting tumor cells in metastatic lesions. Int J Cancer 66(5):607–610

    Article  PubMed  CAS  Google Scholar 

  33. Park YB, Lee SK, Kim DS, Lee J, Lee CH, Song CH (1998) Elevated interleukin-10 levels correlated with disease activity in systemic lupus erythematosus. Clin Exp Rheumatol 16(3):283–288

    PubMed  CAS  Google Scholar 

  34. Hasegawa M, Fujimoto M, Kikuchi K, Takehara K (1997) Elevated serum levels of interleukin 4 (IL-4), IL-10 and IL-13 in patients with systemic sclerosis. J Rheumatol 24(2):328–332

    PubMed  CAS  Google Scholar 

  35. Fayad L, Keating MJ, Reuben JM, O’Brien S, Lee BN, Lerner S et al (2001) Interleukin-6 and interleukin-10 levels in chronic lymphocytic leukemia: correlation with phenotypic characteristics and outcome. Blood 97(1):256–263

    Article  PubMed  CAS  Google Scholar 

  36. van Montfrans C, Camoglio L, van Deventer SJ (1998) Immunotherapy of Crohn’s disease. Mediators Inflamm 7(3):149–152

    Article  PubMed  Google Scholar 

  37. Zou K, Liu S, Xie X, Yi C (2001) Clinical significance and assessment of cytokines in various stages of ulcerative colitis. J Tongji Med Univ 21(4):308–309

    Article  PubMed  CAS  Google Scholar 

  38. Asadullah K, Sterry W, Stephanek K, Jasulaitis D, Leupold M, Audring H et al (1998) IL-10 is a key cytokine in psoriasis. Proof of principle by IL-10 therapy: a new therapeutic approach. J Clin Invest 101(4):783–794

    Article  PubMed  CAS  Google Scholar 

  39. Katsikis PD, Chu CQ, Brennan FM, Maini RN, Feldmann M (1994) Immunoregulatory role of interleukin 10 in rheumatoid arthritis. J Exp Med 179(5):1517–1527

    Article  PubMed  CAS  Google Scholar 

  40. Ishida H, Muchamuel T, Sakaguchi S, Andrade S, Menon S, Howard M (1994) Continuous administration of anti-interleukin 10 antibodies delays onset of autoimmunity in NZB/W F1 mice. J Exp Med 179(5):305–310

    Article  PubMed  CAS  Google Scholar 

  41. Jacob CO, McDevitt HO (1988) Tumor necrosis factor-or in murine autoimmune 'lupus' nephritis. Nature 331(6154):356–358

    Article  PubMed  CAS  Google Scholar 

  42. Postal M, Appenzeller S (2011) The role of tumor necrosis factor-alpha (TNF-α) in the pathogenesis of systemic lupus erythematosus. Cytokine 56(3):537–543

    Article  PubMed  CAS  Google Scholar 

  43. Ravirajan CT, Wang Y, Matis LA, Papadaki L, Griffiths MH, Latchman DS et al (2004) Effect of neutralizing antibodies to IL-10 and C5 on the renal damage caused by a pathogenic human anti-dsDNA antibody. Rheumatology (Oxford) 43(4):442–447

    Article  CAS  Google Scholar 

  44. Yin Z, Bahtiyar G, Zhang N, Liu L, Zhu P, Robert ME et al (2002) IL-10 regulates murine lupus. J Immunol 169(4):2148–2155

    PubMed  CAS  Google Scholar 

  45. Ma L, Chan KW, Trendell-Smith NJ, Wu A, Tian L, Lam AC et al (2005) Systemic autoimmune disease induced by dendritic cells that have captured necrotic but not apoptotic cells in susceptible mouse strains. Eur J Immunol 35(11):3364–3375

    Article  PubMed  CAS  Google Scholar 

  46. Blenman KR, Duan B, Xu Z, Wan S, Atkinson MA, Flotte TR et al (2006) IL-10 regulation of lupus in the NZM2410 murine model. Lab Invest 86(11):1136–1148

    PubMed  CAS  Google Scholar 

  47. Ling GS, Cook HT, Botto M, Lau YL, Huang FP (2011) An essential protective role of IL-10 in the immunological mechanism underlying resistance vs. susceptibility to lupus induction by dendritic cells and dying cells. Rheumatology (Oxford) 50(10):1773–1784

    Article  CAS  Google Scholar 

  48. Mikita N, Ikeda T, Ishiguro M, Furukawa F (2011) Recent advances in cytokines in cutaneous and systemic lupus erythematosus. J Dermatol 38(9):839–849

    PubMed  CAS  Google Scholar 

  49. Balomenos D, Rumold R, Theofilopoulos AN (1998) Interferon-gamma is required for lupus-like disease and lymphoaccumulation in MRL-lpr mice. J Clin Invest 101(2):364–371

    Article  PubMed  CAS  Google Scholar 

  50. Haas C, Ryffel B, Le Hir M (1998) IFN-gamma receptor deletion prevents autoantibody production and glomerulonephritis in lupus-prone (NZB × NZW) F1 mice. J Immunol 160(8):3713–3718

    PubMed  CAS  Google Scholar 

  51. O’Garra A, Chang R, Go N, Hastings R, Haughton G, Howard M (1992) Ly-1 B (B-1) cells are the main source of B cell-derived interleukin 10. Eur J Immunol 22(3):711–717

    Article  PubMed  Google Scholar 

  52. Hayakawa K, Hardy RR, Herzenberg LA (1986) Peritoneal Ly-1 B-cells: genetic control, autoantibody production, increased lambda light chain expression. Eur J Immunol 16(4):450–456

    Article  PubMed  CAS  Google Scholar 

  53. Mohan C, Morel L, Yang P, Wakeland EK (1998) Accumulation of splenic B1a cells with potent antigen-presenting capability in NZM2410 lupus-prone mice. Arthritis Rheum 41(9):1652–1662

    Article  PubMed  CAS  Google Scholar 

  54. Xu Z, Duan B, Croker BP, Wakeland EK, Morel L (2005) Genetic dissection of the murine lupus susceptibility locus Sle2: contributions to increased peritoneal B-1a cells and lupus nephritis map to different loci. J Immunol 175(2):936–943

    PubMed  CAS  Google Scholar 

  55. Brummel R, Lenert P (2005) Activation of marginal zone B cells from lupus mice with type A(D) CpG-oligodeoxynucleotides. J Immunol 174(4):2429–2434

    PubMed  CAS  Google Scholar 

  56. Lenert P, Brummel R, Field EH, Ashman RF (2005) TLR-9 activation of marginal zone B cells in lupus mice regulates immunity through increased IL-10 production. J Clin Immunol 25(1):29–40

    Article  PubMed  CAS  Google Scholar 

  57. Gelati M, Lamperti E, Dufour A, Corsini E, Venegoni E, Milanese C et al (1997) IL-10 production in multiple sclerosis patients, SLE patients and healthy controls: preliminary findings. Ital J Neurol Sci 18(4):191–194

    Article  PubMed  CAS  Google Scholar 

  58. Lacki JK, Samborski W, Mackiewicz SH (1997) Interleukin-10 and interleukin-6 in lupus erythematosus and rheumatoid arthritis, correlations with acute phase proteins. Clin Rheumatol 16(3):275–278

    Article  PubMed  CAS  Google Scholar 

  59. Waszczykowska E, Robak E, Wozniacka A, Narbutt J, Torzecka JD, Sysa-Jedrzejowska A (1999) Estimation of SLE activity based on the serum level of chosen cytokines and superoxide radical generation. Mediators Inflamm 8(2):93–100

    Article  PubMed  CAS  Google Scholar 

  60. Liu TF, Jones BM (1998) Impaired production of IL-12 in system lupus erythematosus. II: IL-12 production in vitro is correlated negatively with serum IL-10, positively with serum IFN-gamma and negatively with disease activity in SLE. Cytokine 10(2):148–153

    Article  PubMed  CAS  Google Scholar 

  61. Hase K, Tani K, Shimizu T, Ohmoto Y, Matsushima K, Sone S (2001) Increased CCR4 expression in active systemic lupus erythematosus. J Leukoc Biol 70(5):749–755

    PubMed  CAS  Google Scholar 

  62. Yang PT, Kasai H, Zhao LJ, Xiao WG, Tanabe F, Ito M (2004) Increased CCR4 expression on circulating CD4 (+) T cells in ankylosing spondylitis, rheumatoid arthritis and systemic lupus erythematosus. Clin Exp Immunol 138(2):342–347

    Article  PubMed  CAS  Google Scholar 

  63. Chun HY, Chung JW, Kim HA, Yun JM, Jeon JY, Ye YM et al (2007) Cytokine IL-6 and IL-10 as biomarkers in systemic lupus erythematosus. J Clin Immunol 27(5):461–466

    Article  PubMed  CAS  Google Scholar 

  64. Mellor-Pita S, Citores MJ, Castejon R, Yebra-Bango M, Tutor-Ureta P, Rosado S et al (2009) Monocytes and T lymphocytes contribute to a predominance of interleukin 6 and interleukin 10 in systemic lupus erythematosus. Cytometry B Clin Cytom 76(4):261–270

    PubMed  Google Scholar 

  65. Liu Y, Zhu T, Cai G, Qin Y, Wang W, Tang G et al (2011) Elevated circulating CD4+ ICOS + Foxp3+ T cells contribute to overproduction of IL-10 and are correlated with disease severity in patients with systemic lupus erythematosus. Lupus 20(6):620–627

    Article  PubMed  CAS  Google Scholar 

  66. Arora V, Verma J, Marwah V, Kumar A, Anand D, Das N (2012) Cytokine imbalance in systemic lupus erythematosus: a study on northern Indian subjects. Lupus 21(6):596–603

    Article  PubMed  CAS  Google Scholar 

  67. Houssiau FA, Lefebvre C, Vanden Berghe M, Lambert M, Devogelaer JP, Renauld JC (1995) Serum interleukin 10 titers in systemic lupus erythematosus reflect disease activity. Lupus 4(5):393–395

    Article  PubMed  CAS  Google Scholar 

  68. El-Sayed M, Nofal E, al Mokadem S, al Makhzangy I, Gaballah H, Akl H (2008) Correlative study of serum Th1/Th2 cytokines levels in patients with systemic lupus erythematosus with SLEDAI. Egypt Dermatol Online J 4(1):3–19

    Google Scholar 

  69. Zhi-Chun L, Qiao-Ling Z, Zhi-Qin L, Xiao-Zhao L, Xiao-xia Z, Rong T (2012) Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) mediates p38 mitogen-activated protein kinase activation and signal transduction in peripheral blood mononuclear cells from patients with lupus nephritis. Inflammation 35(3):935–943

    Article  PubMed  CAS  Google Scholar 

  70. Dhir V, Singh AP, Aggarwal A, Naik S, Misra R (2009) Increased T-lymphocyte apoptosis in lupus correlates with disease activity and may be responsible for reduced T-cell frequency: a cross-sectional and longitudinal study. Lupus 18(9):785–791

    Article  PubMed  CAS  Google Scholar 

  71. Chen J, Shen B, Jiang Y, Jun L, Zhu M, Chen B et al (2013) Analysis of immunoglobulin-like transcripts (ILTs) in lymphocytes with sHLA-G and IL10 from SLE patients. Clin Exp Med 13(2):135–42

    Google Scholar 

  72. Uhm WS, Na K, Song GW, Jung SS, Lee T, Park MH et al (2003) Cytokine balance in kidney tissue from lupus nephritis patients. Rheumatology (Oxford) 42(8):935–938

    Article  CAS  Google Scholar 

  73. Wang Y, Ito S, Chino Y, Goto D, Matsumoto I, Murata H et al (2010) Laser microdissection-based analysis of cytokine balance in the kidneys of patients with lupus nephritis. Clin Exp Immunol 159(1):1–10

    Article  PubMed  CAS  Google Scholar 

  74. Gross JA, Johnston J, Mudri S, Enselman R, Dillon SR, Madden K et al (2000) TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease. Nature 404(6781):995–999

    Article  PubMed  CAS  Google Scholar 

  75. Hondowicz BD, Alexander ST, Quinn WJ 3rd, Pagán AJ, Metzgar MH, Cancro MP et al (2007) The role of BLyS/BLyS receptors in anti-chromatin B cell regulation. Int Immunol 19(4):465–475

    Article  PubMed  CAS  Google Scholar 

  76. Moulin V, Andris F, Thielemans K, Maliszewski C, Urbain J, Moser M (2000) B lymphocytes regulate dendritic cell (DC) function in vivo: increased interleukin 12 production by DCs from B cell-deficient mice results in T helper cell type 1 deviation. J Exp Med 192(4):475–482

    Article  PubMed  CAS  Google Scholar 

  77. Jacobi AM, Odendahl M, Reiter K, Bruns A, Burmester GR, Radbruch A et al (2003) Correlation between circulating CD27 high plasma cells and disease activity in patients with systemic lupus erythematosus. Arthritis Rheum 48(5):1332–1342

    Article  PubMed  Google Scholar 

  78. Ito T, Hanabuchi S, Wang YH, Park WR, Arima K, Bover L et al (2008) Two functional subsets of FOXP3+ regulatory T cells in human thymus and periphery. Immunity 28(6):870–880

    Article  PubMed  CAS  Google Scholar 

  79. Huber S, Gagliani N, Esplugues E, O’Connor W Jr, Huber FJ, Chaudhry A et al (2011) Th17 cells express interleukin-10 receptor and are controlled by Foxp3- and Foxp3+ regulatory CD4+ T cells in an interleukin-10-dependent manner. Immunity 34(4):554–565

    Article  PubMed  CAS  Google Scholar 

  80. Zhao XF, Pan HF, Yuan H, Zhang WH, Li XP, Wang GH et al (2010) Increased serum interleukin 17 in patients with systemic lupus erythematosus. Mol Biol Rep 37(1):81–85

    Article  PubMed  CAS  Google Scholar 

  81. Llorente L, Zou W, Levy Y, Richaud-Patin Y, Wijdenes J, Alcocer-Varela J et al (1995) Role of interleukin 10 in the B lymphocyte hyperactivity and autoantibody production of human systemic lupus erythematosus. J Exp Med 181(3):839–844

    Article  PubMed  CAS  Google Scholar 

  82. Lauwerys BR, Garot N, Renauld JC, Houssiau FA (2000) Interleukin-10 blockade corrects impaired in vitro cellular immune responses of systemic lupus erythematosus patients. Arthritis Rheum 43(9):1976–1981

    Article  PubMed  CAS  Google Scholar 

  83. Llorente L, Richaud-Patin Y, García-Padilla C, Claret E, Jakez-Ocampo J, Cardiel MH et al (2000) Clinical and biologic effects of anti-interleukin-10 monoclonal antibody administration in systemic lupus erythematosus. Arthritis Rheum 43(8):1790–1800

    Article  PubMed  CAS  Google Scholar 

  84. Yuan W, DiMartino SJ, Redecha PB, Ivashkiv LB, Salmon JE (2011) Systemic lupus erythematosus monocytes are less responsive to interleukin-10 in the presence of immune complexes. Arthritis Rheum 63(1):212–218

    Article  PubMed  CAS  Google Scholar 

  85. Johanneson B, Lima G, von Salomé J, Alarcón-Segovia D, Alarcón-Riquelme ME, Collaborative Group on the Genetics of SLE, The BIOMED II Collaboration on the Genetics of SLE and Sjögrens syndrome (2002) A major susceptibility locus for systemic lupus erythemathosus maps to chromosome 1q31. Am J Hum Genet 71(5):1060–1071

    Article  PubMed  CAS  Google Scholar 

  86. Guzowski D, Chandrasekaran A, Gawel C, Palma J, Koenig J, Wang XP et al (2005) Analysis of single nucleotide polymorphisms in the promoter region of interleukin-10 by denaturing high-performance liquid chromatography. J Biomol Tech 16(2):154–166

    PubMed  Google Scholar 

  87. Lazarus M, Hajeer AH, Turner D, Sinnott P, Worthington J, Ollier WE et al (1997) Genetic variation in the interleukin 10 gene promoter and systemic lupus erythematosus. J Rheumatol 24(12):2314–2317

    PubMed  CAS  Google Scholar 

  88. Mok CC, Lanchbury JS, Chan DW, Lau CS (1998) Interleukin-10 promoter polymorphisms in Southern Chinese patients with systemic lupus erythematosus. Arthritis Rheum 41(6):1090–1095

    Article  PubMed  CAS  Google Scholar 

  89. Rood MJ, Keijsers V, van der Linden MW, Tong TQ, Borggreve SE, Verweij CL et al (1999) Neuropsychiatric systemic lupus erythematosus is associated with imbalance in interleukin 10 promoter haplotypes. Ann Rheum Dis 58(2):85–89

    Article  PubMed  CAS  Google Scholar 

  90. Crawley E, Woo P, Isenberg DA (1999) Single nucleotide polymorphic haplotypes of the interleukin-10 5′ flanking region are not associated with renal disease or serology in Caucasian patients with systemic lupus erythematosus. Arthritis Rheum 42(9):2017–2018

    Article  PubMed  CAS  Google Scholar 

  91. van der Linden MW, Westendorp RG, Sturk A, Bergman W, Huizinga TW (2000) High interleukin-10 production in first-degree relatives of patients with generalized but not cutaneous lupus erythematosus. J Investig Med 48(5):327–334

    PubMed  Google Scholar 

  92. Dijstelbloem HM, Hepkema BG, Kallenberg CG, van der Linden MW, Keijsers V, Huizinga TW et al (2002) The R-H polymorphism of FCgamma receptor IIa as a risk factor for systemic lupus erythematosus is independent of single-nucleotide polymorphisms in the interleukin-10 gene promoter. Arthritis Rheum 46(4):1125–1126

    Article  PubMed  CAS  Google Scholar 

  93. D’ Alfonso S, Giordano M, Mellai M, Lanceni M, Barizzone N, Marchini M et al (2002) Association tests with systemic lupus erythematosus (SLE) of IL10 markers indicate a direct involvement of a CA repeat in the 5′ regulatory region. Genes Immun 3(8):454–463

    Article  CAS  Google Scholar 

  94. Chong WP, Ip WK, Wong WH, Lau CS, Chan TM, Lau YL (2004) Association of interleukin-10 promoter polymorphisms with systemic lupus erythematosus. Genes Immun 5(6):484–492

    Article  PubMed  CAS  Google Scholar 

  95. Fei GZ, Svenungsson E, Frostegård J, Padyukov L (2004) The A-1087IL-10 allele is associated with cardiovascular disease in SLE. Atherosclerosis 177(2):409–414

    Article  PubMed  CAS  Google Scholar 

  96. Zhu LJ, Liu ZH, Zeng CH, Chen ZH, Yu C, Li LS (2005) Association of interleukin-10 gene -592A/C polymorphism with the clinical and pathological diversity of lupus nephritis. Clin Exp Rheumatol 23(6):854–860

    PubMed  CAS  Google Scholar 

  97. Lu LY, Cheng HH, Sung PK, Tai MH, Yeh JJ, Chen A (2005) Tumor necrosis factor-beta +252A polymorphism is associated with systemic lupus erythematosus in Taiwan. J Formos Med Assoc 104(8):563–570

    PubMed  CAS  Google Scholar 

  98. Suárez A, López P, Mozo L, Gutiérrez C (2005) Differential effect of IL10 and TNF{alpha} genotypes on determining susceptibility to discoid and systemic lupus erythematosus. Ann Rheum Dis 64(11):1605–1610

    Article  PubMed  CAS  Google Scholar 

  99. Hrycek A, Siekiera U, Cieślik P, Szkróbka W (2005) HLA-DRB1 and -DQB1 alleles and gene polymorphisms of selected cytokines in systemic lupus erythematosus. Rheumatol Int 26(1):1–6

    Article  PubMed  CAS  Google Scholar 

  100. Khoa PD, Sugiyama T, Yokochi T (2005) Polymorphism of interleukin-10 promoter and tumor necrosis factor receptor II in Vietnamese patients with systemic lupus erythematosus. Clin Rheumatol 24(1):11–13

    Article  PubMed  Google Scholar 

  101. Sung YK, Park BL, Shin HD, Kim LH, Kim SY, Bae SC (2006) Interleukin-10 gene polymorphisms are associated with the SLICC/ACR Damage Index in systemic lupus erythematosus. Rheumatology (Oxford) 45(4):400–404

    Article  CAS  Google Scholar 

  102. Hirankarn N, Wongpiyabovorn J, Hanvivatvong O, Netsawang J, Akkasilpa S, Wongchinsri J et al (2006) The synergistic effect of FC gamma receptor IIa and interleukin-10 genes on the risk to develop systemic lupus erythematosus in Thai population. Tissue Antigens 68(5):399–406

    Article  PubMed  CAS  Google Scholar 

  103. Guarnizo-Zuccardi P, Lopez Y, Giraldo M, Garcia N, Rodriguez L, Ramirez L et al (2007) Cytokine gene polymorphisms in Colombian patients with systemic lupus erythematosus. Tissue Antigens 70(5):376–382

    Article  PubMed  CAS  Google Scholar 

  104. Lin PW, Huang CM, Huang CC, Tsai CH, Tsai JJ, Chang CP et al (2007) The association of −627 interleukin-10 promoter polymorphism in Chinese patients with systemic lupus erythematosus. Clin Rheumatol 26(3):298–301

    Article  PubMed  Google Scholar 

  105. Rosado S, Rua-Figueroa I, Vargas JA, Garcia-Laorden MI, Losada-Fernandez I, Martin-Donaire T et al (2008) Interleukin-10 promoter polymorphisms in patients with systemic lupus erythematosus from the Canary Islands. Int J Immunogenet 35(3):235–242

    Article  PubMed  CAS  Google Scholar 

  106. Sobkowiak A, Lianeri M, Wudarski M, Łacki JK, Jagodziński PP (2009) Genetic variation in the interleukin-10 gene promoter in Polish patients with systemic lupus erythematosus. Rheumatol Int 29(8):921–925

    Article  PubMed  CAS  Google Scholar 

  107. Lin YJ, Wan L, Huang CM, Sheu JJ, Chen SY, Lin TH et al (2010) IL-10 and TNF-alpha promoter polymorphisms in susceptibility to systemic lupus erythematosus in Taiwan. Clin Exp Rheumatol 28(3):318–324

    PubMed  Google Scholar 

  108. Zhou M, Ding L, Peng H, Wang B, Huang F, Xu WD et al (2013) Association of the interleukin-10 gene polymorphism (−1082A/G) with systemic lupus erythematosus: a meta-analysis. Lupus 22(2):128–135

    Article  PubMed  CAS  Google Scholar 

  109. Song GG, Choi SJ, Ji JD, Lee YH (2013) Associations between interleukin-10 polymorphisms and susceptibility to systemic lupus erythematosus: a meta-analysis. Hum Immunol 74(3):364–370

    Article  PubMed  CAS  Google Scholar 

  110. Eskdale J, Kube D, Gallagher G (1996) A second polymorphic dinucleotide repeat in the 5′ flanking region of the human IL10 gene. Immunogenetics 45(1):82–83

    Article  PubMed  CAS  Google Scholar 

  111. Eskdale J, Wordsworth P, Bowman S, Field M, Gallagher G (1997) Association between polymorphisms at the human IL-10 locus and systemic lupus erythematosus. Tissue Antigens 49(6):635–639

    Article  PubMed  CAS  Google Scholar 

  112. Mehrian R, Quismorio FP Jr, Strassmann G, Stimmler MM, Horwitz DA, Kitridou RC et al (1998) Synergistic effect between IL-10 and bcl-2 genotypes in determining susceptibility to systemic lupus erythematosus. Arthritis Rheum 41(4):596–602

    Article  PubMed  CAS  Google Scholar 

  113. Alarcón-Riquelme ME, Lindqvist AK, Jonasson I, Johanneson B, Sandino S, Alcocer-Varela J et al (1999) Genetic analysis of the contribution of IL10 to systemic lupus erythematosus. J Rheumatol 26(10):2148–2152

    PubMed  Google Scholar 

  114. Schotte H, Gaubitz M, Willeke P, Tidow N, Assmann G, Domschke W et al (2004) Interleukin-10 promoter microsatellite polymorphisms in systemic lupus erythematosus: association with the anti-Sm immune response. Rheumatology (Oxford) 43(11):1357–1363

    Article  CAS  Google Scholar 

  115. Ou TT, Tsai WC, Chen CJ, Chang JG, Yen JH, Wang WS et al (1998) Genetic analysis of interleukin-10 promoter region in patients with systemic lupus erythematosus in Taiwan. Kaohsiung J Med Sci 14(10):599–606

    PubMed  CAS  Google Scholar 

  116. Nath SK, Harley JB, Lee YH (2005) Polymorphisms of complement receptor 1 and interleukin-10 genes and systemic lupus erythematosus: a meta-analysis. Hum Genet 118(2):225–234

    Article  PubMed  CAS  Google Scholar 

  117. Lin SY, Hsieh SC, Lin YC, Lee CN, Tsai MH, Lai LC et al (2012) A whole genome methylation analysis of systemic lupus erythematosus: hypomethylation of the IL10 and IL1R2 promoters is associated with disease activity. Genes Immun 13(3):214–220

    Article  PubMed  CAS  Google Scholar 

  118. Zhao M, Tang J, Gao F, Wu X, Liang Y, Yin H et al (2010) Hypomethylation of IL10 and IL13 promoters in CD4+ T cells of patients with systemic lupus erythematosus. J Biomed Biotechnol 2010:931018

    PubMed  Google Scholar 

  119. DiMartino SJ, Yuan W, Redecha P, Ivashkiv LB, Salmon JE (2008) Insoluble immune complexes are most effective at triggering IL-10 production in human monocytes and synergize with TLR ligands and C5a. Clin Immunol 127(1):56–65

    Article  PubMed  CAS  Google Scholar 

  120. Cairns AP, Crockard AD, Bell AL (2003) Interleukin-10 receptor expression in systemic lupus erythematosus and rheumatoid arthritis. Clin Exp Rheumatol 21(1):83–86

    PubMed  CAS  Google Scholar 

  121. Valencia-Pacheco G, Layseca-Espinosa E, Niño-Moreno P, Portales-Pérez DP, Baranda L, Rosenstein Y et al (2006) Expression and function of IL-10R in mononuclear cells from patients with systemic lupus erythematosus. Scand J Rheumatol 35(5):368–378

    Article  PubMed  CAS  Google Scholar 

  122. Cui HD, Qi ZM, Yang LL, Qi L, Zhang N, Zhang XL et al (2011) Interleukin-10 receptor expression and signaling were down-regulated in CD4+ T cells of lupus nephritis patients. Clin Exp Immunol 165(2):163–171

    Article  PubMed  CAS  Google Scholar 

  123. Figueroa-Vega N, Galindo-Rodríguez G, Bajaña S, Portales-Pérez D, Abud-Mendoza C, Sánchez-Torres C et al (2006) Phenotypic analysis of IL-10-treated, monocyte-derived dendritic cells in patients with systemic lupus erythematosus. Scand J Immunol 64(6):668–676

    Article  PubMed  CAS  Google Scholar 

  124. Li YM, Chen ZQ, Yao X, Yang AZ, Li AS, Liu DM et al (2010) mRNA expression of chemokine receptors on peripheral blood mononuclear cells and correlation with clinical features in systemic lupus erythematosus patients. Chin Med Sci J 25(3):162–168

    Article  PubMed  CAS  Google Scholar 

  125. Qi ZM, Wang J, Sun ZR, Ma FM, Zhang QR, Hirose S et al (2005) Polymorphism of the mouse gene for the interleukin 10 receptor alpha chain (IL-10ra) and its association with the autoimmune phenotype. Immunogenetics 57(9):697–702

    Article  PubMed  CAS  Google Scholar 

  126. Nakashima H, Akahoshi M, Tanaka Y, Yamaoka K, Ogami E, Nagano S et al (1999) Polymorphisms within the interleukin-10 receptor cDNA gene (IL10R) in Japanese patients with systemic lupus erythematosus. Rheumatology (Oxford) 38(11):1142–1144

    Article  CAS  Google Scholar 

  127. Xu Y, Chen ZQ, Li YM, Gong JQ, Li AS, Chen M et al (2007) Correlation between some Th1 and Th2 cytokine receptor gene polymorphisms and systemic lupus erythematosus in Chinese patients. Int J Dermatol 46(11):1129–1135

    Article  PubMed  Google Scholar 

  128. Hermann J, Gruber S, Neufeld JB, Grundtner P, Graninger M, Graninger WB et al (2009) IL10R1 loss-of-function alleles in rheumatoid arthritis and systemic lupus erythematosus. Clin Exp Rheumatol 27(4):603–608

    PubMed  CAS  Google Scholar 

  129. Gasche C, Grundtner P, Zwirn P, Reinisch W, Shaw SH, Zdanov A et al (2003) Novel variants of the IL-10 receptor 1 affect inhibition of monocyte TNF-alpha production. J Immunol 170(11):5578–5582

    PubMed  CAS  Google Scholar 

  130. Hikami K, Ehara Y, Hasegawa M, Fujimoto M, Matsushita M, Oka T et al (2008) Association of IL-10 receptor 2 (IL10RB) SNP with systemic sclerosis. Biochem Biophys Res Commun 373(3):403–407

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was partly supported by grants from the key program of National Natural Science Foundation of China (30830089) and the Anhui Provincial Natural Science Foundation (11040606M183).

Disclosures

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dong-Qing Ye.

Additional information

Hui Peng and Wei Wang contributed equally to this work and should be considered co-first authors.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Peng, H., Wang, W., Zhou, M. et al. Role of interleukin-10 and interleukin-10 receptor in systemic lupus erythematosus. Clin Rheumatol 32, 1255–1266 (2013). https://doi.org/10.1007/s10067-013-2294-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-013-2294-3

Keywords

Navigation