氧甾醇
生物
胆固醇
炎症
T细胞
内科学
细胞
内分泌学
细胞生物学
免疫系统
免疫学
生物化学
医学
作者
Michela Frascoli,Enxhi Ferraj,Bing Miu,Justin Malin,Nicholas A. Spidale,Jennifer E. Cowan,Susanna C. Shissler,Robert Brink,Ying Xu,Jason G. Cyster,Avinash Bhandoola,Joonsoo Kang,Andrea Reboldi
出处
期刊:Immunity
[Elsevier]
日期:2023-03-01
卷期号:56 (3): 562-575.e6
被引量:9
标识
DOI:10.1016/j.immuni.2023.01.025
摘要
Summary
Dietary components and metabolites have a profound impact on immunity and inflammation. Here, we investigated how sensing of cholesterol metabolite oxysterols by γδ T cells impacts their tissue residency and function. We show that dermal IL-17-producing γδ T (Tγδ17) 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 γδ 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 Tγδ17 cells. Diet-driven increases in oxysterols exacerbate Tγδ17-cell-mediated psoriatic inflammation, dependent on GPR183 on γδ 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 Tγδ17 cells.
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