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

Wenjun Ouyang, Max Löhning, Zhiguang Gao, Mario Assenmacher, Sheila Ranganath, Andreas Radbruch, Kenneth M. Murphy

Research output: Contribution to journalArticlepeer-review

576 Scopus citations

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.

Original languageEnglish
Pages (from-to)27-37
Number of pages11
JournalImmunity
Volume12
Issue number1
DOIs
StatePublished - Jan 2000

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