Format

Send to

Choose Destination
Immunity. 2007 Jul;27(1):89-99. Epub 2007 Jul 19.

Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch.

Author information

1
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA. d.amsen@amc.uva.nl

Abstract

CD4(+) T helper cells differentiate into T helper 1 (Th1) or Th2 effector lineages, which orchestrate immunity to different types of microbes. Both Th1 and Th2 differentiation can be induced by Notch, but what dictates which of these programs is activated in response to Notch is not known. By using T cell-specific gene ablation of the Notch effector RBP-J or the Notch1 and 2 receptors, we showed here that Notch was required on CD4(+) T cells for physiological Th2 responses to parasite antigens. GATA-3 was necessary for Notch-induced Th2 differentiation, and we identified an upstream Gata3 promoter as a direct target for Notch signaling. Moreover, absence of GATA-3 turned Notch from a Th2 inducer into a powerful inducer of Th1 differentiation. Therefore, Gata3 is a critical element determining inductive Th2 differentiation and limiting Th1 differentiation by Notch.

PMID:
17658279
PMCID:
PMC2062505
DOI:
10.1016/j.immuni.2007.05.021
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center