The transcription factor c-Maf is essential for the commitment of IL-17-producing [gamma][delta] T cells

[gamma][delta] T cells that produce the cytokine IL-17 (T[gamma][delta]17 cells) are innate-like mediators of immunity that undergo effector programming in the thymus. While regulators of T[gamma][delta]17 specialization restricted to various V[gamma] subsets are known, a commitment factor essential to all T[gamma][delta]17 cells has remained undefined. In this study, we identified the transcription factor c-Maf as a universal regulator of T[gamma][delta]17 cell differentiation and maintenance. Maf deficiency caused an absolute lineage block at the immature CD24.sup.+CD45RB.sup.lo [gamma][delta] thymocyte stage, which revealed a critical checkpoint in the acquisition of effector functions. Here, c-Maf enforced T[gamma][delta]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-[gamma]-producing [gamma][delta] T cells (T[gamma][delta]1 cells). Furthermore, [gamma][delta] T cell antigen receptor ([gamma][delta]TCR) signal strength tuned c-Maf expression, which indicates that c-Maf is a core node that connects [gamma][delta]TCR signals to T[gamma][delta]17 cell transcriptional programming.