TY - JOUR
T1 - Stat6-independent GATA-3 autoactivation directs IL-4-independent Th2 development and commitment
AU - Ouyang, Wenjun
AU - Löhning, Max
AU - Gao, Zhiguang
AU - Assenmacher, Mario
AU - Ranganath, Sheila
AU - Radbruch, Andreas
AU - Murphy, Kenneth M.
N1 - Funding Information:
We thank S. Agarwal and A. Rao for advice on DNase I hypersensitivity analysis, D. Fenoglio for cell sorting, and T. Geske, S. Höher, R. Siemer, and M. Steinbach for expert technical help. This work was supported by National Institutes of Health grants AI34580 and HL56419 and by the Deutsche Forschungsgemeinschaft through the Sonderforschungsbereich 421, by the Bundesministerium für Forschung und Technologie through grant BEO/21/11340, and by the Senatsverwaltung für Wissenschaft of the state of Berlin. M. L. is a fellow of the Studienstiftung des deutschen Volkes. K. M. M. is an Associate Investigator of the Howard Hughes Medical Institute.
PY - 2000/1
Y1 - 2000/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/0033973582
U2 - 10.1016/S1074-7613(00)80156-9
DO - 10.1016/S1074-7613(00)80156-9
M3 - Article
C2 - 10661403
AN - SCOPUS:0033973582
SN - 1074-7613
VL - 12
SP - 27
EP - 37
JO - Immunity
JF - Immunity
IS - 1
ER -