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.
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.
Xinyan
X
Zhao
Bo
B
Zheng
Yanfang
Y
Huang
Dan
D
Yang
Shoshana
S
Katzman
Chawnshang
C
Chang
Deborah
D
Fowell
Wei-ping
WP
Zeng
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