Notch Simultaneously Orchestrates Multiple Helper T Cell Programs Independently of Cytokine Signals

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2013 Jul 30

PMID 23890069

Citations 85

Authors

Will Bailis

Yumi Yashiro-Ohtani

Terry C Fang

Robin D Hatton

Casey T Weaver

David Artis

Warren S Pear

Affiliations

Soon will be listed here.

Abstract

Two models are proposed to explain Notch function during helper T (Th) cell differentiation. One argues that Notch instructs one Th cell fate over the other, whereas the other posits that Notch function is dictated by cytokines. Here we provide a detailed mechanistic study investigating the role of Notch in orchestrating Th cell differentiation. Notch neither instructed Th cell differentiation nor did cytokines direct Notch activity, but instead, Notch simultaneously regulated the Th1, Th2, and Th17 cell genetic programs independently of cytokine signals. In addition to regulating these programs in both polarized and nonpolarized Th cells, we identified Ifng as a direct Notch target. Notch bound the Ifng CNS-22 enhancer, where it synergized with Tbet at the promoter. Thus, Notch acts as an unbiased amplifier of Th cell differentiation. Our data provide a paradigm for Notch in hematopoiesis, with Notch simultaneously orchestrating multiple lineage programs, rather than restricting alternate outcomes.

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