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 journalArticle

124 Citations (Scopus)

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

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Regulatory T-Lymphocytes
Th17 Cells
Autoimmune Experimental Encephalomyelitis
MAP Kinase Signaling System
trichostatin A
Genes
Chronic Disease
In Vitro Techniques
Therapeutics

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Role of SMAD and non-SMAD signals in the development of Th17 and regulatory T cells. / Lu, Ling; Wang, Julie; Zhang, Feng; Chai, Yang; Brand, David; Wang, Xuehao; Horwitz, David A.; Shi, Wei; Zheng, Song Guo.

In: Journal of Immunology, Vol. 184, No. 8, 15.04.2010, p. 4295-4306.

Research output: Contribution to journalArticle

Lu, L, Wang, J, Zhang, F, Chai, Y, Brand, D, Wang, X, Horwitz, DA, Shi, W & Zheng, SG 2010, 'Role of SMAD and non-SMAD signals in the development of Th17 and regulatory T cells', Journal of Immunology, vol. 184, no. 8, pp. 4295-4306. https://doi.org/10.4049/jimmunol.0903418
Lu, Ling ; Wang, Julie ; Zhang, Feng ; Chai, Yang ; Brand, David ; Wang, Xuehao ; Horwitz, David A. ; Shi, Wei ; Zheng, Song Guo. / Role of SMAD and non-SMAD signals in the development of Th17 and regulatory T cells. In: Journal of Immunology. 2010 ; Vol. 184, No. 8. pp. 4295-4306.
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AU - Horwitz, David A.

AU - Shi, Wei

AU - Zheng, Song Guo

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