| First Author | Frascoli M | Year | 2023 |
| Journal | Immunity | Volume | 56 |
| Issue | 3 | Pages | 562-575.e6 |
| PubMed ID | 36842431 | Mgi Jnum | J:349864 |
| Mgi Id | MGI:7448317 | Doi | 10.1016/j.immuni.2023.01.025 |
| Citation | Frascoli M, et al. (2023) Skin gammadelta T cell inflammatory responses are hardwired in the thymus by oxysterol sensing via GPR183 and calibrated by dietary cholesterol. Immunity 56(3):562-575.e6 |
| abstractText | Dietary components and metabolites have a profound impact on immunity and inflammation. Here, we investigated how sensing of cholesterol metabolite oxysterols by gammadelta T cells impacts their tissue residency and function. We show that dermal IL-17-producing gammadelta T (Tgammadelta17) cells essential for skin-barrier homeostasis require oxysterols sensing through G protein receptor 183 (GPR183) for their development and inflammatory responses. Single-cell transcriptomics and murine reporter strains revealed that GPR183 on developing gammadelta thymocytes is needed for their maturation by sensing medullary thymic epithelial-cell-derived oxysterols. In the skin, basal keratinocytes expressing the oxysterol enzyme cholesterol 25-hydroxylase (CH25H) maintain dermal Tgammadelta17 cells. Diet-driven increases in oxysterols exacerbate Tgammadelta17-cell-mediated psoriatic inflammation, dependent on GPR183 on gammadelta T cells. Hence, cholesterol-derived oxysterols control spatially distinct but biologically linked processes of thymic education and peripheral function of dermal T cells, implicating diet as a focal parameter of dermal Tgammadelta17 cells. |
