c-Maf is an essential commitment factor for IL-17-producing gd T cells [ATAC-seq]

IL-17-producing gd T (Tgd17) cells are early mediators of immunity and autoimmunity that undergo effector programming in the thymus. While Vg subset-restricted regulators of Tgd17 specialization are known, a universal type 17 commitment factor for all gd T cells remains undefined. In this study, we identify the transcription factor c-Maf as an essential and uniform regulator of Tgd17 differentiation and maintenance. The absolute lineage block caused by Maf deficiency reveals a critical effector acquisition checkpoint at the immature CD24+ CD45RBlo gd thymocyte stage. Here, c-Maf enforces Tgd17 identity by promoting chromatin accessibility and activating expression of lineage-defining RORgt and key type 17 program genes, while coordinately antagonizing the negative regulator TCF1, which promotes the alternative IFNg+ Tgd1 fate. During specialization, c-Maf expression is tuned by gdTCR signal strength, implicating c-Maf as a rheostat controlling effector gd T cell generation and connecting gdTCR signals to a core node in the Tgd17 network. Evaluation of differential ATAC-seq accessibilty in Maf-deficient E17-E18 immature fetal Tgd17 thymocytes. The Omni ATAC protocol was performed on replicate samples of immature CD4- CD8- CD3e+ TCRgd+ CD24+ CD45RBlo/- gd thymocytes isolated from Maf+/+ Il7r-Cre and Maf fl/fl Il7r-Cre fetal thymi.