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PMID: 17658278 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Notch directly regulates Gata3 expression during T helper 2 cell differentiation.

Immunity ·Vol. 27 ·No. 1 ·2007-07-00 ·Pages 100-10

Fang TC, Yashiro-Ohtani Y, Del Bianco C, Knoblock DM, Blacklow SC, Pear WS

Abstract

Notch signaling plays multiple roles to direct diverse decisions regarding cell fate during T cell development. During helper T (Th) cell differentiation, Notch is involved in generating optimal Th2 cell responses. Here, we present data investigating how Notch mediates Th2 cell differentiation. Notch showed a CD4(+) T cell intrinsic role in promoting IL-4 expression that required GATA-3. In the absence of Notch signals, Gata3 expression was markedly diminished. Introduction of an activated allele of Notch1 into CD4(+) T cells led to the specific and direct upregulation of a developmentally regulated Gata3 transcript that included the exon 1a sequences. Furthermore, Notch acted in parallel with GATA-3 to synergistically activate IL-4 expression. Together, these data implicate Gata3 as a direct transcriptional Notch target that acts in concert with Notch signaling to generate optimal Th2 cell responses.

MeSH Terms
Animals Cell Differentiation/immunology Cells, Cultured Down-Regulation/immunology GATA3 Transcription Factor/antagonists & inhibitors,biosynthesis,genetics,metabolism Gene Expression Regulation/immunology Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Receptors, Notch/physiology Signal Transduction/immunology Th2 Cells/cytology,immunology,metabolism
Chemicals
GATA3 Transcription Factor Gata3 protein, mouse Receptors, Notch
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Fang Terry C
Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Yashiro-Ohtani Yumi
Del Bianco Cristina
Knoblock Dawson M
Blacklow Stephen C
Pear Warren S
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1074-7613
DOI
10.1016/j.immuni.2007.04.018
Published
2007-07-00
Epub
2007-00-19
Pages
100-10
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC2801546
Subset
IM
Grants
NIAID NIH HHS · R01 AI047833 · United States
NIGMS NIH HHS · T32GM007229 · United States
NCI NIH HHS · R01 CA092433 · United States
NIGMS NIH HHS · T32 GM007229 · United States
NCI NIH HHS · P01 CA119070-020003 · United States
NCI NIH HHS · R01 CA092433-05 · United States
NCI NIH HHS · P01 CA119070-01A19001 · United States
NIAID NIH HHS · R01 AI047833-09 · United States
NCI NIH HHS · P01 CA119070 · United States
External Links
PubMed source DOI: 10.1016/j.immuni.2007.04.018 PMC Full Text View journal details
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