title: The transcription factor GATA3 actively represses RUNX3 protein-regulated production of interferon-gamma.
abstract: The transcription factor GATA3 is crucial for the differentiation of naive CD4(+) T cells into T helper 2 (Th2) cells. Here, we show that deletion of Gata3 allowed the appearance of interferon-gamma (IFN-gamma)-producing cells in the absence of interleukin-12 (IL-12) and IFN-gamma. Such IFN-gamma production was transcription factor T-bet independent. Another T-box-containing transcription factor Eomes, but not T-bet, was induced both in GATA3-deficient CD4(+) T cells differentiated under Th2 cell conditions and in Th2 cells with enforced Runx3 expression, contributing to IFN-gamma production. GATA3 overexpression blocked Runx3-mediated Eomes induction and IFN-gamma production, and GATA3 protein physically interacted with Runx3 protein. Furthermore, we found that Runx3 directly bound to multiple regulatory elements of the Ifng gene and that blocking Runx3 function in either Th1 or GATA3-deficient "Th2" cells results in diminished IFN-gamma production by these cells. Thus, the Runx3-mediated pathway, actively suppressed by GATA3, induces IFN-gamma production in a STAT4- and T-bet-independent manner.
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Yagi
authors.forename: Ilkka S
authors.initials: IS
authors.lastname: Junttila
authors.forename: Gang
authors.initials: G
authors.lastname: Wei
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Urban
authors.forename: Keji
authors.initials: K
authors.lastname: Zhao
authors.forename: William E
authors.initials: WE
authors.lastname: Paul
authors.forename: Jinfang
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017353:Gene Deletion; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D011485:Protein Binding; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; C493730:Runx3 protein, mouse; D007371:Interferon-gamma
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