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Nat Immunol. 2004 Nov;5(11):1157-65. Epub 2004 Oct 10.

Conditional deletion of Gata3 shows its essential function in T(H)1-T(H)2 responses.

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1
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. jfzhu@niaid.nih.gov <jfzhu@niaid.nih.gov>

Abstract

Expression of the transcription factor GATA-3 is strongly associated with T helper type 2 (T(H)2) differentiation, but genetic evidence for its involvement in this process has been lacking. Here, we generated a conditional GATA-3-deficient mouse line. In vitro deletion of Gata3 diminished both interleukin 4 (IL-4)-dependent and IL-4-independent T(H)2 cell differentiation; without GATA-3, T(H)1 differentiation occurred in the absence of IL-12 and interferon-gamma. Gata3 deletion limited the growth of T(H)2 cells but not T(H)1 cells. Deletion of Gata3 from established T(H)2 cells abolished IL-5 and IL-13 but not IL-4 production. In vivo deletion of Gata3 using OX40-Cre eliminated T(H)2 responses and allowed the development of interferon-gamma-producing cells in mice infected with Nippostrongylus brasiliensis. Thus, GATA-3 serves as a principal switch in determining T(H)1-T(H)2 responses.

PMID:
15475959
DOI:
10.1038/ni1128
[Indexed for MEDLINE]
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