4.6 Article

Interaction between GATA-3 and the transcriptional coregulator Pias1 is important for the regulation of Th2 immune responses

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JOURNAL OF IMMUNOLOGY
卷 179, 期 12, 页码 8297-8304

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AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.179.12.8297

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  1. NIAID NIH HHS [R01-AI47263] Funding Source: Medline

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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.

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