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Expressions of IL-22 in circulating CD4+/CD8+ T cells and their correlation with disease activity in SLE patients

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Abstract

Recently, Th17 cell-associated responses have received growing attention; however, the role of IL-22 (a cytokines also produced by Th17 cells) in the pathogenesis of systemic lupus erythematosus (SLE) has not been widely explored. In this study, we analyze the frequencies of IL-22-positive CD4+/CD8+ T cells in peripheral blood mononuclear cells (PBMCs) from patients with SLE and their correlations with disease activity and clinical data. Five-color flow cytometry (FCM) was used to assess IL-22 production of CD4+/CD8+ T cells in PBMCs from 31 patients with SLE and 22 healthy control subjects, following stimulation ex vivo with phorbol 12-myristate 13-acetate and ionomycin for 4 h. Results showed that the percentages of IL-22-positive CD4+ T cells were increased in the PBMCs of patients with SLE compared with healthy control subjects, whereas there were no significant differences in the percentages of IL-22-positive CD8+ T cells. There was a strong positive correlation between the proportion of CD4+ T cells expressing IL-22 and SLEDAI score (r s = 0.65, P < 0.001). Furthermore, the frequencies of IL-22-positive CD4+ T cells were significantly higher in patients with SLE with nephritis than those without nephritis (Z = −2.72, P < 0.01). In conclusion, increased frequencies of IL-22-positive CD4+ T cells in patients with SLE and positive correlation with SLEDAI score and lupus nephritis suggest that this cytokine may be implicated in the pathogenesis of the disease.

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References

  1. Chung Y, Yang X, Chang SH, Ma L, Tian Q, Dong C (2006) Expression and regulation of IL-22 in the IL-17-producing CD4+ T lymphocytes. Cell Res 16:902–907

    Article  PubMed  CAS  Google Scholar 

  2. Liang SC, Tan XY, Luxenberg DP, Karim R, Dunussi-Joannopoulos K, Collins M, Fouser LA (2006) Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med 203:2271–2279

    Article  PubMed  CAS  Google Scholar 

  3. Norian LA, Rodriguez PC, O’Mara LA, Zabaleta J, Ochoa AC, Cella M, Allen PM (2009) Tumor-infiltrating regulatory dendritic cells inhibit CD8+ T cell function via l-arginine metabolism. Cancer Res 69:3086–3094

    Article  PubMed  CAS  Google Scholar 

  4. Duhen T, Geiger R, Jarrossay D, Lanzavecchia A, Sallusto F (2009) Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells. Nat Immunol 10:857–863

    Article  PubMed  CAS  Google Scholar 

  5. Trifari S, Kaplan CD, Tran EH, Crellin NK, Spits H (2009) Identification of a human helper T cell population that has abundant production of interleukin22 and is distinct from T(H) 17, T(H)1 and T(H)2 cells. Nat Immunol 10:864–871

    Article  PubMed  CAS  Google Scholar 

  6. Radaeva S, Sun R, Pan HN, Hong F, Gao B (2004) Interleukin 22 (IL-22) plays a protective role in T cell-mediated murine hepatitis: IL-22 is a survival factor for hepatocytes via STAT3 activation. Hepatology 39:1332–1342

    Article  PubMed  CAS  Google Scholar 

  7. Zenewicz LA, Yancopoulos GD, Valenzuela DM, Murphy AJ, Stevens S, Flavell RA (2008) Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease. Immunity 29:947–957

    Article  PubMed  CAS  Google Scholar 

  8. Ikeuchi H, Kuroiwa T, Hiramatsu N, Kaneko Y, Hiromura K, Ueki K, Nojima Y (2005) Expression of interleukin-22 in rheumatoid arthritis: potential role as a proinflammatory cytokine. Arthritis Rheum 52:1037–1046

    Article  PubMed  CAS  Google Scholar 

  9. Geboes L, Dumoutier L, Kelchtermans H, Schurgers E, Mitera T, Renauld JC, Matthys P (2009) Proinflammatory role of the Th17 cytokine interleukin-22 in collagen-induced arthritis in C57BL/6 mice. Arthritis Rheum 60:390–395

    Article  PubMed  CAS  Google Scholar 

  10. Hochberg MC, For the Diagnostic, Therapeutic Criteria Committee of the American College of Rheumatology (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40:1725

    Article  PubMed  CAS  Google Scholar 

  11. Wong CK, Lit LC, Tam LS, Li EK, Wong PT, Lam CW (2008) Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: implications for Th17-mediated inflammation in auto-immunity. Clin Immunol 127:385–393

    Article  PubMed  CAS  Google Scholar 

  12. Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH (1992) Derivation of the SLEDAI. A disease activity index for lupus patients. The committee on prognosis studies in SLE. Arthritis Rheum 35:630–640

    Article  PubMed  CAS  Google Scholar 

  13. Shen H, Goodall JC, Hill Gaston JS (2009) Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis. Arthritis Rheum 60:1647–1656

    Article  PubMed  CAS  Google Scholar 

  14. Schmechel S, Konrad A, Diegelmann J, Glas J, Wetzke M, Paschos E, Lohse P, Göke B, Brand S (2008) Linking genetic susceptibility to Crohn’s disease with Th17 cell function: IL-22 serum levels are increased in Crohn’s disease and correlate with disease activity and IL23R genotype status. Inflam Bowel Dis 14:204–212

    Article  Google Scholar 

  15. Yang J, Chu Y, Yang X, Gao D, Zhu L, Yang X, Wan L, Li M (2009) Th17 and natural Treg cell population dynamics in systemic lupus erythematosus. Arthritis Rheum 60:1472–1483

    Article  PubMed  Google Scholar 

  16. Zheng Y, Danilenko DM, Valdez P, Kasman I, Eastham-Anderson J, Wu J, Ouyang W (2007) Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature 445:648–651

    Article  PubMed  CAS  Google Scholar 

  17. Billerbeck E, Kang YH, Walker L, Lockstone H, Grafmueller S, Fleming V, Flint J, Willberg CB, Bengsch B, Seigel B, Ramamurthy N, Zitzmann N, Barnes EJ, Thevanayagam J, Bhagwanani A, Leslie A, Oo YH, Kollnberger S, Bowness P, Drognitz O, Adams DH, Blum HE, Thimme R, Klenerman P (2010) Analysis of CD161 expression on human CD8+ T cells defines a distinct functional subset with tissue-homing properties. Proc Natl Acad Sci USA 107:3006–3011

    Article  PubMed  Google Scholar 

  18. Lo YH, Torii K, Saito C, Furuhashi T, Maeda A, Morita A (2010) Serum IL-22 correlates with psoriatic severity and serum IL-6 correlates with susceptibility to phototherapy. J Dermatol Sci 58:225–227

    Article  PubMed  CAS  Google Scholar 

  19. Pan HF, Zhao XF, Yuan H, Zhang WH, Li XP, Wang GH, Wu GC, Tang XW, Li WX, Li LH, Feng JB, Hu CS, Ye DQ (2009) Decreased serum IL-22 levels in patients with systemic lupus erythematosus. Clin Chim Acta 401:179–180

    Article  PubMed  CAS  Google Scholar 

  20. Cheng F, Guo Z, Xu H, Yan D, Li Q (2009) Decreased plasma IL22 levels, but not increased IL17 and IL23 levels, correlate with disease activity in patients with systemic lupus erythematosus. Ann Rheum Dis 68:604–606

    Article  PubMed  CAS  Google Scholar 

  21. Ziesché E, Scheiermann P, Bachmann M, Sadik CD, Hofstetter C, Zwissler B, Pfeilschifter J, Mühl H (2009) Dexamethasone suppresses interleukin-22 associated with bacterial infection in vitro and in vivo. Clin Exp Immunol 157:370–376

    Article  PubMed  Google Scholar 

  22. McKinley L, Alcorn JF, Peterson A, Dupont RB, Kapadia S, Logar A, Henry A, Irvin CG, Piganelli JD, Ray A, Kolls JK (2008) TH17 cells mediate steroid-resistant airway inflammation and airway hyperresponsiveness in mice. J Immunol 181:4089–4097

    PubMed  CAS  Google Scholar 

  23. Kang HK, Liu M, Datta SK (2007) Low-dose peptide tolerance therapy of lupus generates plasmacytoid dendritic cells that cause expansion of autoantigen-specific regulatory T cells and contraction of inflammatory Th17 cells. J Immunol 178:7849–7858

    PubMed  CAS  Google Scholar 

  24. Kyttaris VC, Zhang Z, Kuchroo VK, Oukka M, Tsokos GC (2010) Cutting edge: IL-23 receptor deficiency prevents the development of lupus nephritis in C57BL/6-lpr/lpr mice. J Immunol 184:4605–4609

    Article  PubMed  CAS  Google Scholar 

  25. Zhang Z, Kyttaris VC, Tsokos GC (2009) The role of IL-23/IL-17 axis in lupus nephritis. J Immunol 183:3160–3169

    Article  PubMed  CAS  Google Scholar 

  26. Liang SC, Nickerson-Nutter C, Pittman DD, Carrier Y, Goodwin DG, Shields KM, Lambert AJ, Schelling SH, Medley QG, Ma HL, Collins M, Dunussi-Joannopoulos K, Fouser LA (2010) IL-22 induces an acute-phase response. J Immunol 185:5531–5538

    Article  PubMed  CAS  Google Scholar 

  27. Li HH, Cheng HH, Sun KH, Wei CC, Li CF, Chen WC, Wu WM, Chang MS (2008) Interleukin-20 targets renal mesangial cells and is associated with lupus nephritis. Clin Immunol 129:277–285

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

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

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The authors declared no competing interests.

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Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, 230032, Hefei, Anhui, People’s Republic of China

    Wei-Zi Qin, Li-Li Chen, Hai-Feng Pan, Rui-Xue Leng, Chao Wang, Ruo-Jie Li, Song Wang & Dong-Qing Ye

  2. The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, 230601, Hefei, Anhui, People’s Republic of China

    Zhi-Min Zhai & Hui-Ping Wang

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  1. Wei-Zi Qin
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  2. Li-Li Chen
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  3. Hai-Feng Pan
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Correspondence to Dong-Qing Ye.

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W.-Z. Qin and L.–L. Chen contributed equally to this work and should be regarded as co-first authors.

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Qin, WZ., Chen, LL., Pan, HF. et al. Expressions of IL-22 in circulating CD4+/CD8+ T cells and their correlation with disease activity in SLE patients. Clin Exp Med 11, 245–250 (2011). https://doi.org/10.1007/s10238-011-0134-9

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  • DOI: https://doi.org/10.1007/s10238-011-0134-9

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