小柯机器人

美国马萨诸塞大学Andrea Reboldi等研究人员合作发现，皮肤γδ T细胞的炎症反应通过GPR183的氧甾醇感应在胸腺中被连接并被膳食胆固醇校准。这一研究成果于2023年2月24日在线发表在国际学术期刊《免疫》上。

研究人员揭示了γδ T细胞对胆固醇代谢物氧甾醇的感知如何影响其组织驻留和功能。研究人员发现，真皮产生IL-17的γδT（Tγδ17）细胞对皮肤屏障稳态至关重要，它们的发育和炎症反应需要通过G蛋白受体183（GPR183）来感知氧甾醇。单细胞转录组学和小鼠报告菌株显示，发育中的γδ胸腺细胞上的GPR183通过感知髓质胸腺上皮细胞衍生的氧甾醇而成熟。

在皮肤中，表达氧甾醇酶胆固醇25-羟化酶（CH25H）的基底角质形成细胞维持真皮Tγδ17细胞。饮食驱动增加氧甾醇来加剧Tγδ17细胞介导的银屑病炎症，这依赖于γδ T细胞上的GPR183。因此，胆固醇衍生的氧甾醇控制着胸腺教育和真皮T细胞外周功能的空间不同但生物学上相关的过程，这意味着饮食是真皮Tγδ17细胞的一个焦点参数。

附：英文原文

Title: Skin γδ T cell inflammatory responses are hardwired in the thymus by oxysterol sensing via GPR183 and calibrated by dietary cholesterol

Author: Michela Frascoli, Enxhi Ferraj, Bing Miu, Justin Malin, Nicholas A. Spidale, Jennifer Cowan, Susanna C. Shissler, Robert Brink, Ying Xu, Jason G. Cyster, Avinash Bhandoola, Joonsoo Kang, Andrea Reboldi

Issue&Volume: 2023-02-24

Abstract: Dietary components and metabolites have a profound impact on immunity and inflammation.Here, we investigated how sensing of cholesterol metabolite oxysterols by γδ T cellsimpacts their tissue residency and function. We show that dermal IL-17-producing γδT (Tγδ17) cells essential for skin-barrier homeostasis require oxysterols sensingthrough G protein receptor 183 (GPR183) for their development and inflammatory responses.Single-cell transcriptomics and murine reporter strains revealed that GPR183 on developingγδ thymocytes is needed for their maturation by sensing medullary thymic epithelial-cell-derivedoxysterols. In the skin, basal keratinocytes expressing the oxysterol enzyme cholesterol25-hydroxylase (CH25H) maintain dermal Tγδ17 cells. Diet-driven increases in oxysterolsexacerbate Tγδ17-cell-mediated psoriatic inflammation, dependent on GPR183 on γδ T cells.Hence, cholesterol-derived oxysterols control spatially distinct but biologicallylinked processes of thymic education and peripheral function of dermal T cells, implicatingdiet as a focal parameter of dermal Tγδ17 cells.

DOI: 10.1016/j.immuni.2023.01.025

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00037-7

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