| First Author | Zuberbuehler MK | Year | 2019 |
| Journal | Nat Immunol | Volume | 20 |
| Issue | 1 | Pages | 73-85 |
| PubMed ID | 30538336 | Mgi Jnum | J:282653 |
| Mgi Id | MGI:6381295 | Doi | 10.1038/s41590-018-0274-0 |
| Citation | Zuberbuehler MK, et al. (2019) The transcription factor c-Maf is essential for the commitment of IL-17-producing gammadelta T cells. Nat Immunol 20(1):73-85 |
| abstractText | gammadelta T cells that produce the cytokine IL-17 (Tgammadelta17 cells) are innate-like mediators of immunity that undergo effector programming in the thymus. While regulators of Tgammadelta17 specialization restricted to various Vgamma subsets are known, a commitment factor essential to all Tgammadelta17 cells has remained undefined. In this study, we identified the transcription factor c-Maf as a universal regulator of Tgammadelta17 cell differentiation and maintenance. Maf deficiency caused an absolute lineage block at the immature CD24(+)CD45RB(lo) gammadelta thymocyte stage, which revealed a critical checkpoint in the acquisition of effector functions. Here, c-Maf enforced Tgammadelta17 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 gammadelta T cells (Tgammadelta1 cells). Furthermore, gammadelta T cell antigen receptor (gammadeltaTCR) signal strength tuned c-Maf expression, which indicates that c-Maf is a core node that connects gammadeltaTCR signals to Tgammadelta17 cell transcriptional programming. |
