Title

Janus-kinase-3-dependent signals induce chromatin remodeling at the Ifng locus during T helper 1 cell differentiation

UMMS Affiliation

Department of Pathology

Publication Date

6-14-2008

Document Type

Article

Subjects

Animals; CD4-Positive T-Lymphocytes; Cell Differentiation; *Chromatin Assembly and Disassembly; Cytokines; Epigenesis, Genetic; Interferon-gamma; Janus Kinase 3; Mice; Mice, Mutant Strains; Promoter Regions, Genetic; STAT Transcription Factors; STAT5 Transcription Factor; Signal Transduction; Th1 Cells

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Differentiation of naive CD4+ T cells into T helper type 1 (Th1) effector cells requires both T cell receptor (TCR) signaling and cytokines such as interleukin-12 and interferon gamma (IFN-gamma). Here, we report that a third cytokine signal, mediated by the Janus family tyrosine kinase 3 (Jak3) and signal transducer and activator of transcription 5 (STAT5) pathway, is also required for Th1 cell differentiation. In the absence of Jak3-dependent signals, naive CD4+ T cells proliferate robustly but produce little IFN-gamma after Th1 cell polarization in vitro. This defect is not due to reduced activation of STAT1 or STAT4 or to impaired upregulation of the transcription factor T-bet. Instead, we find that T-bet binding to the Ifng promoter is greatly diminished in the absence of Jak3-dependent signals, correlating with a decrease in Ifng promoter accessibility and histone acetylation. These data indicate that Jak3 regulates epigenetic modification and chromatin remodeling of the Ifng locus during Th1 cell differentiation.

Rights and Permissions

Citation: Immunity. 2008 Jun;28(6):763-73. Link to article on publisher's site

DOI of Published Version

10.1016/j.immuni.2008.04.016

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Immunity

PubMed ID

18549798