Journal
IMMUNITY
Volume 12, Issue 1, Pages 27-37Publisher
CELL PRESS
DOI: 10.1016/S1074-7613(00)80156-9
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Funding
- NHLBI NIH HHS [HL56419] Funding Source: Medline
- NIAID NIH HHS [AI34580] Funding Source: Medline
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P50HL056419] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [U01AI034580, U19AI034580] Funding Source: NIH RePORTER
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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.
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