Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Critical Role of IL-21 in Modulating Th17 Responses and Regulatory T Cells in Behet Disease.
Geri1, Guillaume, Terrier1, Benjamin, Rosenzwajg1, Michelle, Wechsler2, Bertrand, Boutin1, Du Le, Bodaghi1, Bahram, Tran1, Tu-Ahn
Behçet disease (BD) is a systemic vasculitis of unknown origin. Infectious or environmental factors and Th1 cells producing IFN-g have been involved in its pathogenesis, but these findings remain controversial.
To determine the implication of Th1, Th17 and regulatory T cells in the pathogenesis of BD.
Forty BD patients (20 active untreated [aBD] and 20 treated and inactive [iBD]) fulfilling the international diagnostic criteria and 20 healthy donors (HD) were included. Flow cytometric analysis of peripheral blood mononuclear cells and purified CD4+ T cells was performed for cell surface markers, intracellular production of cytokines and FoxP3 transcription factor. Measurements of cytokine levels in serum and culture supernatants were also performed.
A marked enrichment in IL-17A-producing CD4+ CD45RO+CCR6+ T cells (Th17) was found in peripheral blood of aBD compared with iBD and HD (3.1 vs. 1.0 and 0.6 %, P<0.0001 for both), whereas IFN-g producing CD4+ and CD8+ T cells did not differ between aBD and HD. Th17 expansion was more pronounced in cerebrospinal fluid of aBD with central nervous system involvement. CD4+CD25highCD127-FoxP3+ T cell subset was decreased in aBD compared to HD (1.78 vs. 3.2%, P=0.02). We found an increase in serum IL-21 in aBD compared with iBD and HD whereas no significant difference was noted for others cytokines promoting Th17 differentiation. Expansion of IL-1249-producing CD4+ T cells was observed in aBD compared with iBD and HD (5.5 vs. 2.8 and 1.8 %, P=0.002 and P<0.0001, respectively), that correlated positively with Th17 expansion (r2=0.43; P<0.0001) and negatively with activated Tregs (r2=0.45, P=0.009). Stimulation with anti-CD3/CD28 of purified CD4+ T cells, with human recombinant IL-21, significantly increased Th17 cells and decreased FoxP3 expression. The blockade of IL-21 using IL-21R/Fc chimera markedly decreased production of IL-17A and increased FoxP3 expression in sorted CD4+ T cells.
Taken together, these results are the first to demonstrate the implication of IL-21 in the pathogenesis of BD. IL-21 may exert a critical role in modulating Th17 responses and regulatory T cells in BD, and represent a potential target for novel therapy.
To cite this abstract, please use the following information:
Geri, Guillaume, Terrier, Benjamin, Rosenzwajg, Michelle, Wechsler, Bertrand, Boutin, Du Le, Bodaghi, Bahram, et al; Critical Role of IL-21 in Modulating Th17 Responses and Regulatory T Cells in Behet Disease. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1249