Rheumatology International

, Volume 32, Issue 9, pp 2731–2736

Disturbed Th17/Treg balance in patients with rheumatoid arthritis

Original Article

Abstract

Proinflammatory Th17 cells and CD4+CD25+ regulatory T (Treg) cells are two newly identified T lymphocyte subsets, which have opposite effects on autoimmunity and inflammation. To assess the Th17/Treg pattern and cytokine microenvironment in peripheral blood of patients with RA, we included 66 RA patients and 20 healthy volunteers. Of all these subjects, peripheral Th17 and Treg frequencies were analyzed by flow cytometry (FCM) and the plasma levels of interleukin (IL)-17, 23, 6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1 were detected by ELISA. The results demonstrated that RA patients revealed an obvious increase in peripheral Th17 frequencies and levels of Th17-related cytokines (IL-17, IL-23, IL-6, TNF-α) while a significant decrease in Treg frequencies and Treg-related cytokine (TGF-β1) levels when compared with healthy people. Our study indicated that development of RA is associated with peripheral Th17/Treg imbalance and characterized by a proinflammatory cytokine microenvironment, which supports continuing generation of Th17 cells.

Keywords

Rheumatoid arthritis Th17 cells Regulatory T cells Autoimmunity Inflammation Inflammatory cytokine microenvironment 

References

  1. 1.
    Firestein GS (2003) Evolving concepts of rheumatoid arthritis. Nature 423:356–361PubMedCrossRefGoogle Scholar
  2. 2.
    McInnes IB, Schett G (2007) Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol 7:429–442PubMedCrossRefGoogle Scholar
  3. 3.
    Falgarone G, Duclos M, Boissier MC (2007) TNF-α antagonists in rheumatoid arthritis patients seen in everyday practice. Joint Bone Spine 74:523–526PubMedCrossRefGoogle Scholar
  4. 4.
    Bettelli E, Oukka M, Kuchroo VK (2007) T(H)-17 cells in the circle of immunity and autoimmunity. Nat Immunol 8:345–350PubMedCrossRefGoogle Scholar
  5. 5.
    Marie-Christophe B, Eric A, Geraldine F et al (2008) Shifting the imbalance from Th1/Th2 to Th17/treg: The changing rheumatoid arthritis paradigm. Joint Bone Spine 75:373–375CrossRefGoogle Scholar
  6. 6.
    Arnett FC, Edworthy SM, Bloch DA et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324PubMedCrossRefGoogle Scholar
  7. 7.
    Prevoo ML, van’t Hof MA, Kuper HH et al (1995) Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 38:44–48PubMedCrossRefGoogle Scholar
  8. 8.
    Manoury-Schwartz B, Chiocchia G, Bessis N et al (1997) High susceptibility to collagen-induced arthritis in mice lacking IFN-gamma receptors. J Immunol 158:5501–5506PubMedGoogle Scholar
  9. 9.
    Boissier MC, Chiocchia G, Bessis N et al (1995) Biphasic effect of interferongamma in murine collagen-induced arthritis. Eur J Immunol 25:1184–1190PubMedCrossRefGoogle Scholar
  10. 10.
    Eastaff-Leung N, Mabarrack N, Barbour A et al (2010) Foxp3+ regulatory T cells, Th17 effector cells, and cytokine environment in inflammatory bowel disease. J Clin Immunol 30:80–89PubMedCrossRefGoogle Scholar
  11. 11.
    Nistala K, Moncrieffe H, Newton KR et al (2008) Interleukin-17—producing T cells are enriched in the joints of children with arthritis, but have a reciprocal relationship to regulatory T cell numbers. Arthritis Rheum 58:875–887PubMedCrossRefGoogle Scholar
  12. 12.
    Chengl X, Yu X, Ding Y-J et al (2008) The Th17/Treg imbalance in patients with acute coronary syndrome. Clin Immunol 127:89–97CrossRefGoogle Scholar
  13. 13.
    Paradowska A, Maśliński W, Grzybowska-Kowalczyk A et al (2007) The function of interleukin 17 in the pathogenesis of rheumatoid arthritis. Arch Immunol Ther Exp 55:329–334CrossRefGoogle Scholar
  14. 14.
    Kim KW, Cho ML, Park MK et al (2005) Increased interleukin-17 production via a phosphoinositide 3-kinase/Akt and nuclear factor κB-dependent pathway in patients with rheumatoid arthritis. Arthritis Res Ther 7:R139–R148PubMedCrossRefGoogle Scholar
  15. 15.
    Berg WB, Miossec P (2009) IL-17 as a future therapeutic target for rheumatoid arthritis. Nat Rev Rheumatol 5:549–553PubMedCrossRefGoogle Scholar
  16. 16.
    Lubberts E (2008) IL-17/Th17 targeting: on the road to prevent chronic destructive arthritis? Cytokine 41:84–91PubMedCrossRefGoogle Scholar
  17. 17.
    Hori S, Nomura T, Sakaguchi S (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299:1057–1061PubMedCrossRefGoogle Scholar
  18. 18.
    Abdulahad WH, Stegeman CA, van der Geld YM et al (2007) Functional defect of circulating regulatory CD4 T cells in patients with Wegener’s granulomatosis in remission. Arthritis Rheum 56:2080–2091PubMedCrossRefGoogle Scholar
  19. 19.
    Venken K, Hellings N, Liblau R et al (2010) Disturbed regulatory T cell homeostasis in multiple sclerosis. Trends Mol Med 16:58–68PubMedCrossRefGoogle Scholar
  20. 20.
    Wright GP, Notley CA, Xue SA et al (2009) Adoptive therapy with redirected primary regulatory T cells results in antigen-specific suppression of arthritis. Proc Natl Acad Sci USA 106:19078–19083PubMedCrossRefGoogle Scholar
  21. 21.
    Morgan ME, Flierman R, van Duivenvoorde LM et al (2005) Effective treatment of collagen-induced arthritis by adoptive transfer of CD25+ regulatory T cells. Arthritis Rheum 52:2212–2221PubMedCrossRefGoogle Scholar
  22. 22.
    Bettelli E, Carrier Y, Gao W et al (2006) Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441:235–238PubMedCrossRefGoogle Scholar
  23. 23.
    Kurts C (2008) Th17 cells: a third subset of CD4+ T effector cells involved in organ-specific autoimmunity. Nephrol Dial Transplant 23:816–819PubMedCrossRefGoogle Scholar
  24. 24.
    Wilson NJ, Boniface K, Chan JR et al (2007) Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol 8:950–957PubMedCrossRefGoogle Scholar
  25. 25.
    Fontenot JD, Gavin MA, Rudensky AY (2003) Foxp3 programs the development and function of CD4+ CD25+ regulatory T cells. Nat Immunol 4:330–336PubMedCrossRefGoogle Scholar
  26. 26.
    Acosta-Rodriguez EV, Napoletani G, Lanzavecchia A et al (2007) Interleukins 1β and 6 but not transforming growth factor-β are essential for the differentiation of interleukin 17-producing human T helper cells. Nat Immunol 8:942PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Department of Laboratory MedicineWest China Hospital, Sichuan UniversityChengduThe People’s Republic of China
  2. 2.Department of NephrologyWest China Hospital, Sichuan UniversityChengduThe People’s Republic of China

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