Smad2 Positively Regulates the Generation of Th17 Cells

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2010 Jul 30

PMID 20667820

Citations 54

Authors

Gustavo J Martinez

Zhengmao Zhang

Joseph M Reynolds

Shinya Tanaka

Yeonseok Chung

Ting Liu

Elizabeth Robertson

Xia Lin

Xin-Hua Feng

Chen Dong

Affiliations

Soon will be listed here.

Abstract

Development of Foxp3(+) regulatory T cells and pro-inflammatory Th17 cells from naive CD4(+) T cells requires transforming growth factor-β (TGF-β) signaling. Although Smad4 and Smad3 have been previously shown to regulate Treg cell induction by TGF-β, they are not required in the development of Th17 cells. Thus, how TGF-β regulates Th17 cell differentiation remains unclear. In this study, we found that TGF-β-induced Foxp3 expression was significantly reduced in the absence of Smad2. More importantly, Smad2 deficiency led to reduced Th17 differentiation in vitro and in vivo. In the experimental autoimmune encephalomyelitis model, Smad2 deficiency in T cells significantly ameliorated disease severity and reduced generation of Th17 cells. Furthermore, we found that Smad2 associated with retinoid acid receptor-related orphan receptor-γt (RORγt) and enhanced RORγt-induced Th17 cell generation. These results demonstrate that Smad2 positively regulates the generation of inflammatory Th17 cells.

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