Stat6-independent GATA-3 autoactivation directs IL-4-independent Th2 development and commitment. NLM AIDSLINE Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.

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Stat6-independent GATA-3 autoactivation directs IL-4-independent Th2 development and commitment.

Immunity. 2000 Jan;12(1):27-37. Unique Identifier : AIDSLINE MED/20125019
Ouyang W; Lohning M; Gao Z; Assenmacher M; Ranganath S; Radbruch A; Murphy KM; Department of Pathology and Center for Immunology, Howard Hughes; Medical Institute, Washington University School of Medicine, St.; Louis, Missouri 63110, USA.


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.


Keywords: JOURNAL ARTICLE Animal Chromatin/METABOLISM DNA-Binding Proteins/BIOSYNTHESIS/GENETICS/*METABOLISM Interleukin-4/BIOSYNTHESIS/*METABOLISM Mice Mice, Transgenic Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Th1 Cells/METABOLISM Th2 Cells/*CYTOLOGY/METABOLISM *Trans-Activation (Genetics) Trans-Activators/BIOSYNTHESIS/GENETICS/*METABOLISM/*PHYSIOLOGYKWDjournalarticleanimalchromatin/metabolismdna-bindingproteins/biosynthesis/genetics/KWDmetabolisminterleukin-4/biosynthesis/KWDmetabolismmicemice,transgenicsupport,non-uKWDsKWDgov'tsupport,uKWDsKWDgov't,pKWDhKWDsKWDth1cells/metabolismth2cells/KWDcytology/metabolismKWDtrans-activation(genetics)trans-activators/biosynthesis/genetics/KWDmetabolism/KWDphysiology
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