title: Stat6-independent GATA-3 autoactivation directs IL-4-independent Th2 development and commitment.
abstract: The initial source of IL-4-inducing Th2 development and the mechanism of stable Th2 commitment remain obscure. We found the reduced level of IL-4 production in Stat6-deficient T cells to be significantly higher than in Th1 controls. Using a novel cell surface affinity matrix technique, we found that IL-4-secreting Stat6-deficient T cells stably expressed GATA-3 and Th2 phenotype. Introducing GATA-3 into Stat6-deficient T cells completely restored Th2 development, inducing c-Maf, Th2-specific DNase I hypersensitive sites in the IL-4 locus, and Th2 cytokine expression. The fact that GATA-3 fully reconstitutes Th2 development in Stat6-deficient T cells indicates it is a master switch in Th2 development. Finally, GATA-3 exerts Stat6-independent autoactivation, creating a feedback pathway stabilizing Th2 commitment.
authors.affiliation: Department of Pathology and Center for Immunology, Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: W
authors.initials: W
authors.lastname: Ouyang
authors.forename: M
authors.initials: M
authors.lastname: Löhning
authors.forename: Z
authors.initials: Z
authors.lastname: Gao
authors.forename: M
authors.initials: M
authors.lastname: Assenmacher
authors.forename: S
authors.initials: S
authors.lastname: Ranganath
authors.forename: A
authors.initials: A
authors.lastname: Radbruch
authors.forename: K M
authors.initials: KM
authors.lastname: Murphy
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D050990:GATA3 Transcription Factor; D015847:Interleukin-4 / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D050800:STAT6 Transcription Factor; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology* / Q000378:metabolism; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D015533:Transcriptional Activation
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D015847:Interleukin-4