The transcription factor c-Maf is essential for the commitment of IL-17-producing ?? T cells.

ABSTRACT: ?? T cells that produce the cytokine IL-17 (T??17 cells) are innate-like mediators of immunity that undergo effector programming in the thymus. While regulators of T??17 specialization restricted to various V? subsets are known, a commitment factor essential to all T??17 cells has remained undefined. In this study, we identified the transcription factor c-Maf as a universal regulator of T??17 cell differentiation and maintenance. Maf deficiency caused an absolute lineage block at the immature CD24+CD45RBlo ?? thymocyte stage, which revealed a critical checkpoint in the acquisition of effector functions. Here, c-Maf enforced T??17 cell identity by promoting chromatin accessibility and expression of key type 17 program genes, notably Rorc and Blk, while antagonizing the transcription factor TCF1, which promotes interferon-?-producing ?? T cells (T??1 cells). Furthermore, ?? T cell antigen receptor (??TCR) signal strength tuned c-Maf expression, which indicates that c-Maf is a core node that connects ??TCR signals to T??17 cell transcriptional programming.

SUBMITTER: Zuberbuehler MK 

PROVIDER: S-EPMC6294311 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature