Role of SMAD and non-SMAD signals in the development of Th17 and regulatory T cells

Ling Lu, Julie Wang, Feng Zhang, Yang Chai, David Brand, Xuehao Wang, David A. Horwitz, Wei Shi, Song Guo Zheng

Research output: Contribution to journalArticlepeer-review

141 Scopus citations

Abstract

Whereas TGF-β is essential for the development of peripherally induced Foxp3+ regulatory T cells (iTreg cells) and Th17 cells, the intracellular signaling mechanism by which TGF-β regulates development of both cell subsets is less understood. In this study, we report that neither Smad2 nor Smad3 gene deficiency abrogates TGF-β-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-β signaling pathways during iTreg and Th17 cell development might lead to the development of therapies in treating autoimmune and other chronic inflammatory diseases.

Original languageEnglish (US)
Pages (from-to)4295-4306
Number of pages12
JournalJournal of Immunology
Volume184
Issue number8
DOIs
StatePublished - Apr 15 2010

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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