Batf stabilizes Th17 cell development via impaired Stat5 recruitment of Ets1‐Runx1 complexes.

Although the activator protein‐1 (AP‐1) factor Batf is required for Th17 cell development, its mechanisms of action to underpin the Th17 program are incompletely understood. Here, we find that Batf ensures Th17 cell identity in part by restricting alternative gene programs through its actions to restrain IL‐2 expression and IL‐2‐induced Stat5 activation. This, in turn, limits Stat5‐dependent recruitment of Ets1‐Runx1 factors to Th1‐ and Treg‐cell‐specific gene loci. Thus, in addition to pioneering regulatory elements in Th17‐specific loci, Batf acts indirectly to inhibit the assembly of a Stat5‐Ets1‐Runx1 complex that enhances the transcription of Th1‐ and Treg‐cell‐specific genes. These findings unveil an important role for Stat5‐Ets1‐Runx1 interactions in transcriptional networks that define alternate T cell fates and indicate that Batf plays an indispensable role in both inducing and maintaining the Th17 program through its actions to regulate the competing actions of Stat5‐assembled enhanceosomes that promote Th1‐ and Treg‐cell developmental programs. Synopsis: In addition to its function as a pioneering transcription factor in Th17 development, Batf suppresses alternative T cell fates by down‐regulating IL‐2 receptor components thereby diminishing Stat5 activation and limiting the assembly of a Stat5‐Ets1‐Runx1 enhancer complex that promotes Th1– and Treg–specifying gene expression. Batf inhibits IL‐2 expression early in Th17 development and limits IL‐2R and Stat5 expression in late stage Th17 cells.Batf impairs Stat5‐dependent recruitment of Ets1 and Runx1 to Th1 and Treg‐cell gene loci, thus forming an enhanceosome that promotes lineage‐specifying gene transcription.Sustained Batf expression is essential to prevent deviation to alternative cell fates and stabilize the Th17 phenotype. [ABSTRACT FROM AUTHOR]