Role of SMAD and Non-SMAD Signals in the Development of Th17 and Regulatory T Cells

被引：160

作者：

Lu, Ling ^{[1
,4
]}

Wang, Julie ^{[1
]}

Zhang, Feng ^{[4
]}

Chai, Yang ^{[2
]}

Brand, David ^{[5
]}

Wang, Xuehao ^{[4
]}

Horwitz, David A. ^{[1
]}

Shi, Wei ^{[3
]}

Zheng, Song Guo ^{[1
]}

机构：

[1] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Div Rheumatol,Dept Med, Los Angeles, CA 90033 USA

[2] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Ctr Craniofacial Mol Biol,Sch Dent, Los Angeles, CA 90033 USA

[3] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Dev Biol & Regenerat Med Program,Saban Res Inst, Los Angeles, CA 90033 USA

[4] Nanjing Med Univ, Affiliated Hosp 1, Key Lab Living Donor Liver Transplantat, Nanjing 210029, Peoples R China

[5] Vet Affairs Med Ctr, Res Serv, Memphis, TN 38104 USA

来源：

JOURNAL OF IMMUNOLOGY | 2010年 / 184卷 / 08期

基金：

美国国家卫生研究院; 中国国家自然科学基金;

关键词：

EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; TRANSCRIPTION FACTOR FOXP3; TGF-BETA; CUTTING EDGE; RETINOIC ACID; IFN-GAMMA; EX-VIVO; INDUCTION; EXPRESSION; IL-2;

D O I：

10.4049/jimmunol.0903418

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Whereas TGF-beta is essential for the development of peripherally induced Foxp3(+) regulatory T cells (iTreg cells) and Th17 cells, the intracellular signaling mechanism by which TGF-beta regulates development of both cell subsets is less understood. In this study, we report that neither Smad2 nor Smad3 gene deficiency abrogates TGF-beta-dependent iTreg induction by a deacetylase inhibitor trichostatin A in vivo, although the loss of the Smad2 or Smad3 gene partially reduces iTreg induction in vitro. Similarly, SMAD2 and SMAD3 have a redundant role in development of Th17 in vitro and in experimental autoimmune encephalomyelitis. In addition, ERK and/or JNK pathways were shown to be involved in regulating iTreg cells, whereas the p38 pathway predominately modulated Th17 and experimental autoimmune encephalomyelitis induction. Therefore, selective targeting of these intracellular TGF-beta signaling pathways during iTreg and Th17 cell development might lead to the development of therapies in treating autoimmune and other chronic inflammatory diseases. The Journal of Immunology, 2010, 184: 4295-4306.

引用

页码：4295 / 4306

页数：12

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