Cutting Edge: All-Trans Retinoic Acid Sustains the Stability and Function of Natural Regulatory T Cells in an Inflammatory Milieu

被引:192
作者
Zhou, Xiaohui [1 ,2 ]
Kong, Ning [1 ,3 ]
Wang, Julie [1 ]
Fan, Huiming [2 ]
Zou, Hejian [3 ]
Horwitz, David [1 ,4 ]
Brand, David
Liu, Zhongmin [2 ]
Zheng, Song Guo [1 ]
机构
[1] Univ So Calif, Div Rheumatol, Los Angeles, CA 90033 USA
[2] Tongji Univ, Shanghai E Hosp, Immune Tolerance Ctr, Shanghai 200120, Peoples R China
[3] Fudan Univ, Huashan Hosp, Shanghai 200433, Peoples R China
[4] Vet Affairs Med Ctr, Res Serv, Memphis, TN 38104 USA
基金
中国国家自然科学基金; 美国国家卫生研究院;
关键词
TGF-BETA; ADOPTIVE TRANSFER; TH17; CELLS; SUPPRESSION; INDUCTION; MICE; IL-2; SELF;
D O I
10.4049/jimmunol.1000598
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Recent studies have demonstrated that plasticity of naturally occurring CD4(+)Foxp3(+) regulatory T cells (nTregs) may account for their inability to control chronic inflammation in established autoimmune diseases. All-trans retinoic acid (atRA), the active derivative of vitamin A, has been demonstrated to promote Foxp3(+) Treg differentiation and suppress Th17 development. In this study, we report a vital role of atRA in sustaining the stability and functionality of nTregs in the presence of IL-6. We found that nTregs treated with atRA were resistant to Th17 and other Th cell conversion and maintained Foxp3 expression and suppressive activity in the presence of IL-6 in vitro. atRA decreased IL-6R expression and signaling by nTregs. Of interest, adoptive transfer of nTregs even from arthritic mice treated with atRA suppressed progression of established collagen-induced arthritis. We suggest that nTregs treated with atRA may represent a novel treatment strategy to control established chronic immune-mediated inflammatory diseases. The Journal of Immunology, 2010, 185: 2675-2679.
引用
收藏
页码:2675 / 2679
页数:5
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