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

Details

Serval ID
serval:BIB_1B55C8394758
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Direct regulation of Gata3 expression determines the T helper differentiation potential of Notch
Journal
Immunity
Author(s)
Amsen  D., Antov  A., Jankovic  D., Sher  A., Radtke  F., Souabni  A., Busslinger  M., McCright  B., Gridley  T., Flavell  R. A.
ISSN
1074-7613 (Print)
Publication state
Published
Issued date
07/2007
Volume
27
Number
1
Pages
89-99
Notes
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't --- Old month value: Jul
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.
Keywords
Animals Base Sequence Cell Differentiation/*immunology Cells, Cultured GATA3 Transcription Factor/biosynthesis/*metabolism/physiology Humans Immunoglobulin J Recombination Signal Sequence-Binding Protein/deficiency/genetics/physiology Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Molecular Sequence Data Receptors, Notch/*physiology Signal Transduction/immunology T-Lymphocytes, Helper-Inducer/*cytology/*immunology/metabolism Th1 Cells/cytology/immunology/metabolism Th2 Cells/cytology/immunology/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 11:39
Last modification date
20/08/2019 12:52
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