Interaction between GATA-3 and the transcriptional coregulator Pias1 is important for the regulation of Th2 immune responses.
Th2 cytokine expression is dependent on the transcription factor GATA-3. However, the molecular interactions of GATA-3 leading to Th2 cytokine gene activation have not been well characterized. Here, we reported a number of GATA-3 associated proteins in Th2 cells, and one of such proteins Pias1 functioned as a positive transcriptional coregulator for GATA-3. When overexpressed in Th2 cells, Pias1 enhanced the expression of IL-13, and to lesser degrees, IL-4 and -5. Conversely, Pias1 siRNA down-regulated the Th2 cytokine expression. In Leishmania major infection, manipulating Pias1 expression in parasite-reactive CD4 T cells altered severity of disease caused by Th2 responses. Mechanistically, Pias1 markedly potentiated GATA-3-mediated activation of the IL-13 promoter by facilitating the recruitment of GATA-3 to the promoter. In contrast, IL-5 promoter was modestly enhanced by Pias1 and no effect was observed on IL-4 promoter. Thus, both promoter activation and additional mechanisms are responsible for regulation by Pias1.
Zhao
Xinyan
X
David H. Smith Center for Vaccine Biology and Immunology, Aab Institute for Biomedical Sciences, Department of Microbiology, University of Rochester School of Medicine and Dentistry, NY 14642, USA.
Zheng
Bo
B
Huang
Yanfang
Y
Yang
Dan
D
Katzman
Shoshana
S
Chang
Chawnshang
C
Fowell
Deborah
D
Zeng
Wei-ping
WP
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000235:genetics; D050990:GATA3 Transcription Factor / Q000378:metabolism*; D006801:Humans; D007109:Immunity / Q000235:genetics*; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D018320:Leishmania major; D016773:Leishmaniasis, Cutaneous / Q000235:genetics / Q000276:immunology; D051379:Mice; D011401:Promoter Regions, Genetic; D050828:Protein Inhibitors of Activated STAT / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D012190:Retroviridae / Q000235:genetics; D018418:Th2 Cells / Q000276:immunology*; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
D016207:Cytokines; D050990:GATA3 Transcription Factor; D018793:Interleukin-13; D015848:Interleukin-5; C494211:Pias1 protein, mouse; D050828:Protein Inhibitors of Activated STAT; D034741:RNA, Small Interfering; D015847:Interleukin-4