期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 128, 期 3, 页码 655-664出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2011.05.029
关键词
Behcet disease; T(H)17; T(H)1; regulatory T cells; IL-21; vasculitis; autoimmunity
资金
- Direction Regionale des Affaires Sanitaires et Sociales (DRASS)
- Fondation pour la Recherche Medicale (FRM)
- Agence Nationale pour la Recherche sur le Sida et les Hepatites (ANRS)
- Bristol-Myers Squibb
- Sanofi-Aventis
- Pfizer
- Vifor Pharma
- Servier
- Roche
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 TH(1)7 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. (J Allergy Clin Immunol 2011; 128: 655-64.)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据