T cell factor-1 negatively regulates expression of IL-17 family of cytokines and protects mice from experimental autoimmune encephalomyelitis

Qing Yu, Archna Sharma, Amalendu Ghosh, Jyoti Misra Sen

Research output: Contribution to journalArticle

Abstract

Activated CD4 T cells are associated with protective immunity and autoimmunity. The manner in which the inflammatory potential of T cells and resultant autoimmunity is restrained is poorly understood. In this article, we demonstrate that T cell factor-1 (TCF1) negatively regulates the expression of IL-17 and related cytokines in activated CD4 T cells. We show that TCF1 does not affect cytokine signals and expression of transcription factors that have been shown to regulate Th17 differentiation. Instead, TCF1 regulates IL-17 expression, in part, by binding to the regulatory regions of the Il17 gene. Moreover, TCF1-deficient Th17 CD4 T cells express higher levels of IL-7Rα, which potentially promotes their survival and expansion in vivo. Accordingly, TCF1-deficient mice are hyperresponsive to experimental autoimmune encephalomyelitis. Thus, TCF1, a constitutively expressed T cell-specific transcription factor, is a critical negative regulator of the inflammatory potential of TCR-activated T cells and autoimmunity.

Original languageEnglish (US)
Pages (from-to)3946-3952
Number of pages7
JournalJournal of Immunology
Volume186
Issue number7
DOIs
StatePublished - Apr 1 2011
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

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