Abstract
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.
© 2016 Masuda et al.
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*
Substances
-
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