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.

Automated summary

This study reveals that the activator protein-1 (AP-1) factor Batf ensures Th17 cell identity by restraining IL-2 expression and IL-2-induced Stat5 activation, thereby inhibiting the transcription of Th1 and Treg cell-specific genes. In addition to its role in regulating Th17-specific loci, Batf indirectly inhibits the assembly of a Stat5-Ets1-Runx1 complex, which enhances the transcription of Th1 and Treg cell-specific genes. These findings highlight the importance of Stat5-Ets1-Runx1 interactions in determining T cell fate and underscore the crucial role of Batf in both inducing and maintaining the Th17 program.