The Bcl6 target gene microRNA-21 promotes Th2 differentiation by a T cell intrinsic pathway

Mol Immunol. 2013 Jul;54(3-4):435-42. doi: 10.1016/j.molimm.2013.01.006. Epub 2013 Feb 13.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Cell Differentiation / genetics
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Inflammation / genetics
  • Inflammation / metabolism
  • Inflammation / pathology
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins c-bcl-6
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism
  • Th2 Cells / cytology
  • Th2 Cells / metabolism
  • Th2 Cells / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Bcl6 protein, mouse
  • DNA-Binding Proteins
  • MIRN21 microRNA, mouse
  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-6
  • Repressor Proteins
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Transcription Factors