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

被引：591
作者：
Ouyang, WJ
Löhning, M
Gao, ZG
Assenmacher, M
Ranganath, S
Radbruch, A
Murphy, KM
机构：
[1] Deutsch Rhemaforschungszentrum, D-10115 Berlin, Germany
[2] Washington Univ, Sch Med, Howard Hughes Med Inst, Dept Pathol, St Louis, MO 63110 USA
[3] Washington Univ, Sch Med, Howard Hughes Med Inst, Ctr Immunol, St Louis, MO 63110 USA
[4] Miltenyi Biotec, D-51429 Bergisch Gladbach, Germany
[5] Humboldt Univ, Charite, Dept Expt Rheumatol, D-10115 Berlin, Germany
来源：
IMMUNITY | 2000年 / 12卷 / 01期
关键词：
D O I：
10.1016/S1074-7613(00)80156-9
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
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.
引用
收藏
页码：27 / 37
页数：11
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