Smad2 positively regulates the generation of Th17 cells

Gustavo J. Martinez, Zhengmao Zhang, Joseph M. Reynolds, Shinya Tanaka, Yeonseok Chung, Ting Liu, Elizabeth Robertson, Xia Lin, Xin Hua Feng, Chen Dong

Research output: Contribution to journalArticlepeer-review

76 Citations (Scopus)


Development of Foxp3+ regulatoryTcells 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.

Original languageEnglish
Pages (from-to)29039-29043
Number of pages5
JournalJournal of Biological Chemistry
Issue number38
Publication statusPublished - Sept 17 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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