1. The Bcl6 target gene microRNA-21 promotes Th2 differentiation by a T cell intrinsic pathway
- Author
-
Sawant, Deepali V., Wu, Hao, Kaplan, Mark H., and Dent, Alexander L.
- Subjects
- *
T cell differentiation , *GENE targeting , *MICRORNA , *CELLULAR signal transduction , *INFLAMMATION , *GENETIC transcription - Abstract
Abstract: The transcriptional repressor Bcl6 is a critical regulator of T helper cell fate, and inhibits Th2-type inflammation. We have found that microRNA-21 (miR-21) is a novel target gene for Bcl6 in Treg cells. Bcl6 represses and Stat3 activates miR-21 transcription through a Stat3 binding element in the promoter, indicating opposing regulation of miR-21 by the two transcription factors via the same DNA site. Ectopic expression of miR-21 promoted Th2 differentiation in non-polarized T cells. The pro-Th2 activity of miR-21 was associated with increased Gata3 expression and decreased expression of the miR-21 target gene Sprouty1. Increased miR-21 promoted Th2 and Treg gene expression in wild-type Tregs. MiR-21 could thus help promote the Th2 bias of Bcl6-deficient conventional T cells and Treg cells. MiR21 expression is increased in Th2-type inflammation, and our results define miR-21 as a critical target of Bcl6, thus providing a new link between Bcl6 and Th2 inflammation. Finally, our results reveal a novel T cell autonomous role for miR-21 in promoting Th2 differentiation. [Copyright &y& Elsevier]
- Published
- 2013
- Full Text
- View/download PDF