Critical role of IL-21 in modulating TH17 and regulatory T cells in Behcet disease.

Authors: Geri, G  Terrier, B  Rosenzwajg, M  Wechsler, B  Touzot, M  Seilhean, D  Tran, TA  Bodaghi, B  Musset, L  Soumelis, V  Klatzmann, D  Cacoub, P  Saadoun, D 
Citation: Geri G, etal., J Allergy Clin Immunol. 2011 Sep;128(3):655-64. Epub 2011 Jul 2.
Pubmed: (View Article at PubMed) PMID:21724243
DOI: Full-text: DOI:10.1016/j.jaci.2011.05.029

BACKGROUND: Behcet disease (BD) is a chronic systemic inflammatory disorder of unknown etiology. OBJECTIVE: To determine the nature of T cells driving inflammatory lesions in BD. METHODS: T cell homeostasis and cytokines production were analyzed in peripheral blood and brain inflammatory lesions from 45 adult patients with BD (active and untreated BD [n = 25] and patients in remission [n = 20]) and 20 healthy donors, using Luminex, flow cytometry, immunohistochemistry, and immunofluorescence analysis. RESULTS: We found a marked increase in T(H)17 cells and a decrease in the frequency of CD4(+) forkhead box P3(+) regulatory T cells (Tregs) in peripheral blood that were induced by IL-21 production and that correlate with BD activity. The addition of serum from patients with active BD in a sorted CD4(+) T cells culture of healthy donors induced a significant and dose-dependent production of IL-17A and a decrease in forkhead box P3 expression. We demonstrated the presence of IL-21- and IL-17A-producing T cells within the cerebrospinal fluid, brain parenchyma inflammatory infiltrates, and intracerebral blood vessels from patients with active BD and central nervous system involvement. The stimulation of CD4(+) T cells with IL-21 increased T(H)17 and T(H)1 differentiation and decreased the frequency of Treg cells. Conversely, IL-21 blockade with an IL-21R-Fc restored the T(H)17 and Treg homeostasis in patients with BD. CONCLUSION: We provided here the first evidence of the critical role of IL-21 in driving inflammatory lesions in BD by promoting T(H)17 effectors and suppressing Treg cells. IL-21 represents a promising target for novel therapy in BD.


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CRRD Object Information
CRRD ID: 6892926
Created: 2012-08-16
Species: All species
Last Modified: 2012-08-16
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.