Opposing actions of IL-2 and IL-21 on Th9 differentiation correlate with their differential regulation of BCL6 expression.

ABSTRACT: Interleukin 9 (IL-9) is a γc-family cytokine that is highly produced by T-helper 9 (Th9) cells and regulates a range of immune responses, including allergic inflammation. Here we show that IL-2-JAK3-STAT5 signaling is required for Th9 differentiation, with critical STAT5 binding sites in the Il9 (the gene encoding IL-9) promoter. IL-2 also inhibited B cell lymphoma 6 (BCL6) expression, and overexpression of BCL6 impaired Th9 differentiation. In contrast, IL-21 induced BCL6 and diminished IL-9 expression in wild-type but not Bcl6(-/-) cells, and Th9 differentiation was increased in Il21(-/-) and Il21r(-/-) T cells. Interestingly, BCL6 bound in proximity to many STAT5 and STAT6 binding sites, including at the Il9 promoter. Moreover, there was increased BCL6 and decreased STAT binding at this

SUBMITTER: Liao W 

PROVIDER: S-EPMC3948278 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature