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研究阐明CD8+Trm细胞产生机制
作者:小柯机器人 发布时间:2020/7/9 9:47:20

美国明尼苏达大学Stephen C. Jameson研究组取得最新进展。他们发现通过嘌呤能受体P2RX7感知ATP,且增强CD8 + 组织驻留记忆(Trm)细胞对细胞因子TGF-β的敏感性来促进CD8 + Trm细胞的产生。相关论文于2020年7月7日发表于《免疫》。

他们显示P2RX7通过增强TGF-β的CD8 + T细胞感应来支持Trm细胞产生,这对于组织驻留是必需的。P2RX7缺陷Trm细胞在非淋巴组织中逐渐衰退,并表达失调的Trm特异性标记。P2RX7是通过钙调神经磷酸酶信号转导,有效再表达受体TGF-βRII所必需的。

强制的Tgfbr2表达挽救了P2RX7缺陷的Trm细胞产生,并且P2RX7激动剂和拮抗剂决定了TGF-β的敏感性。强制Tgfbr2还挽救了P2RX7缺陷的Trm细胞线粒体功能。长期的Trm细胞维持需要持续的P2RX7信号转导,这表明P2RX7信号转导可驱动屏障位点的诱导和CD8 + T细胞的持久性。

据介绍,TrmCD8 + T细胞在屏障组织中介导保护性免疫,但促进Trm细胞产生的因素知之甚少。嘌呤能受体P2RX7对细胞外三磷酸腺苷(eATP)的感知是再循环CD8 + T细胞记忆所必需的,但其在Trm细胞中的作用尚不清楚。

附:英文原文

Title: Sensing of ATP via the Purinergic Receptor P2RX7 Promotes CD8+ Trm Cell Generation by Enhancing Their Sensitivity to the Cytokine TGF-β

Author: Henrique Borges da Silva, Changwei Peng, Haiguang Wang, Kelsey M. Wanhainen, Chaoyu Ma, Sharon Lopez, Alexander Khoruts, Nu Zhang, Stephen C. Jameson

Issue&Volume: 2020-07-07

Abstract: Tissue-resident memory (Trm) CD8+ T cells mediate protective immunity in barrier tissues, but the cues promoting Trmcell generation are poorly understood. Sensing of extracellular adenosine triphosphate(eATP) by the purinergic receptor P2RX7 is needed for recirculating CD8+ T cell memory, but its role for Trm cells is unclear. Here we showed that P2RX7 supportedTrm cell generation by enhancing CD8+ T cell sensing of TGF-β, which was necessary for tissue residency. P2RX7-deficientTrm cells progressively decayed in non-lymphoid tissues and expressed dysregulatedTrm-specific markers. P2RX7 was required for efficient re-expression of the receptorTGF-βRII through calcineurin signaling. Forced Tgfbr2 expression rescued P2RX7-deficient Trm cell generation, and TGF-β sensitivity wasdictated by P2RX7 agonists and antagonists. Forced Tgfbr2 also rescued P2RX7-deficient Trm cell mitochondrial function. Sustained P2RX7 signalingwas required for long-term Trm cell maintenance, indicating that P2RX7 signaling drivesinduction and CD8+ T cell durability in barrier sites.

DOI: 10.1016/j.immuni.2020.06.010

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30265-X

期刊信息

Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新if:21.522
官方网址:https://www.cell.com/immunity/home
投稿链接:https://www.editorialmanager.com/immunity/default.aspx