JunB controls intestinal effector programs in regulatory T cells

Abstract

Foxp3-expressing regulatory T (Treg) cells are critical mediators of immunological tolerance to both self and microbial antigens. Tregs activate context-dependent transcriptional programs to adapt effector function to specific tissues; however, the factors controlling tissue-specific gene expression in Tregs remain unclear. Here, we find that the AP-1 transcription factor JunB enables the environmental adaptation of Tregs by facilitating tissue-specific transcriptional programming. Treg-specific ablation of JunB results in immune dysregulation characterized by enhanced colonic T cell accumulation and cytokine production; however – in contrast to its classical binding-partner BATF – JunB is dispensable for both effector Tregs and the majority of Treg subsets. Rather, JunB activates a transcriptional program facilitating the maintenance of CD25- Tregs – including follicular Tregs – and a separate effector program in colonic Tregs that includes the cytolytic molecules Granzymes A and B. Therefore, JunB is a novel and essential regulator of tissue-specific Treg effector programming.