Arid5a regulates naive CD4+ T cell fate through selective stabilization of Stat3 mRNA

J Exp Med. 2016 Apr 4;213(4):605-19. doi: 10.1084/jem.20151289. Epub 2016 Mar 28.


Balance in signal transducer and activator of transcription (STAT) activation is a key factor in regulating the fate of naive CD4(+)T cells. Here, we demonstrate that AT-rich interactive domain-containing protein 5a (Arid5a) in T cells directs naive CD4(+)T cells to differentiate into inflammatory CD4(+)T cells, especially Th17 cells, through selective stabilization of Stat3(but not Stat1 and Stat5) mRNA in an IL-6-dependent manner. Loss of Arid5a in T cells led to reduction of STAT3 level under Th17-polarizing conditions, whereas STAT1 and STAT5 in Arid5a-deficient T cells were highly activated compared with those of WT T cells under the same conditions. These cells displayed the feature of antiinflammatory (Il10-expressing) CD4(+)T cells. Thus, we show a T cell-intrinsic role of Arid5a on fate decisions of naive CD4(+)T cells through selective stabilization of Stat3 mRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology*
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology
  • Mice
  • Mice, Knockout
  • RNA Stability / genetics
  • RNA Stability / immunology*
  • RNA, Messenger / genetics
  • RNA, Messenger / immunology*
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / immunology
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / immunology*
  • STAT5 Transcription Factor / genetics
  • STAT5 Transcription Factor / immunology
  • Th17 Cells / cytology
  • Th17 Cells / immunology*
  • Transcription Factors / genetics
  • Transcription Factors / immunology*


  • Arid5a protein, mouse
  • DNA-Binding Proteins
  • IL10 protein, mouse
  • Interleukin-6
  • RNA, Messenger
  • STAT1 Transcription Factor
  • STAT3 Transcription Factor
  • STAT5 Transcription Factor
  • Stat1 protein, mouse
  • Stat3 protein, mouse
  • Transcription Factors
  • Interleukin-10