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

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 (II10-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.