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J Biol Chem. 2013 Sep 20;288(38):27423-33. doi: 10.1074/jbc.M113.497248. Epub 2013 Aug 9.

The transcription factor Twist1 limits T helper 17 and T follicular helper cell development by repressing the gene encoding the interleukin-6 receptor α chain.

Author information

1
From the Department of Pediatrics, Herman B. Wells Center for Pediatric Research and.

Abstract

Cytokine responsiveness is a critical component of the ability of cells to respond to the extracellular milieu. Transcription factor-mediated regulation of cytokine receptor expression is a common mode of altering responses to the external environment. We identify the transcription factor Twist1 as a component of a STAT3-induced feedback loop that controls IL-6 signals by directly repressing Il6ra. Human and mouse T cells lacking Twist1 have an increased ability to differentiate into Th17 cells. Mice with a T cell-specific deletion of Twist1 demonstrate increased Th17 and T follicular helper cell development, early onset experimental autoimmune encephalomyelitis, and increased antigen-specific antibody responses. Thus, Twist1 has a critical role in limiting both cell-mediated and humoral immunity.

KEYWORDS:

Autoimmunity; Differentiation; Inflammation; Interleukin; STAT Transcription Factor; STAT3; T Cell Biology; T Helper Cell; Transcription Factors

PMID:
23935104
PMCID:
PMC3779737
DOI:
10.1074/jbc.M113.497248
[Indexed for MEDLINE]
Free PMC Article

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