| Autor: |
Zuberbuehler, Matthew K., Parker, Morgan E., Wheaton, Joshua D., Espinosa, Jaclyn R., Salzler, Harmony R., Park, Eunchong, Ciofani, Maria |
| Zdroj: |
Nature Immunology; January 2019, Vol. 20 Issue: 1 p73-85, 13p |
| Abstrakt: |
γδ T cells that produce the cytokine IL-17 (Tγδ17 cells) are innate-like mediators of immunity that undergo effector programming in the thymus. While regulators of Tγδ17 specialization restricted to various Vγ subsets are known, a commitment factor essential to all Tγδ17 cells has remained undefined. In this study, we identified the transcription factor c-Maf as a universal regulator of Tγδ17 cell differentiation and maintenance. Mafdeficiency caused an absolute lineage block at the immature CD24+CD45RBloγδ thymocyte stage, which revealed a critical checkpoint in the acquisition of effector functions. Here, c-Maf enforced Tγδ17 cell identity by promoting chromatin accessibility and expression of key type 17 program genes, notably Rorcand Blk, while antagonizing the transcription factor TCF1, which promotes interferon-γ-producing γδ T cells (Tγδ1 cells). Furthermore, γδ T cell antigen receptor (γδTCR) signal strength tuned c-Maf expression, which indicates that c-Maf is a core node that connects γδTCR signals to Tγδ17 cell transcriptional programming. |
| Databáze: |
Supplemental Index |
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