Sensing of ATP via the Purinergic Receptor P2RX7 Promotes CD8(+) Trm Cell Generation by Enhancing Their Sensitivity to the Cytokine TGF-β.
Sensing of ATP via the Purinergic Receptor P2RX7 Promotes CD8(+) Trm Cell Generation by Enhancing Their Sensitivity to the Cytokine TGF-β.
复制标题
DOI：
10.1016/j.immuni.2020.06.010
复制
发表时间：
2020-07-14
期刊：
影响因子：
32.4
通讯作者：
Jameson SC
中科院分区：
文献类型：
--
作者：
Borges da Silva H;Peng C;Wang H;Wanhainen KM;Ma C;Lopez S;Khoruts A;Zhang N;Jameson SC
组织驻留记忆（Trm）CD 8 + T细胞介导屏障组织中的保护性免疫，但促进Trm细胞生成的线索知之甚少。嘌呤能受体P2 RX 7对细胞外三磷酸腺苷（eATP）的感知是再循环CD 8 + T细胞记忆所必需的，但其对Trm细胞的作用尚不清楚。在这里，我们表明P2 RX 7通过增强TGF-β的CD 8 + T细胞感应来支持Trm细胞生成，这是组织驻留所必需的。P2 RX 7缺陷型Trm细胞在非淋巴组织中逐渐衰退，并表达失调的Trm特异性标志物。P2 RX 7通过钙调神经磷酸酶信号传导对受体TGF-βRII的有效再表达是必需的。强制的Tgfbr 2表达挽救了P2 RX 7缺陷型Trm细胞的产生，并且TGF-β敏感性由P2 RX 7激动剂和拮抗剂决定。强制Tgfbr 2也挽救了P2 RX 7缺陷型Trm细胞线粒体功能。持续的P2 RX 7信号传导是长期Trm细胞维持所需的，表明P2 RX 7信号传导驱动屏障部位的诱导和CD 8 + T细胞耐久性。Borges da Silva等人报道，细胞外ATP受体P2 RX 7通过诱导TGF-β信号传导途径促进病毒特异性组织驻留记忆（Trm）CD 8 +T细胞的产生。此外，Trm细胞的长期维持依赖于连续的P2 RX 7信号传导。
Tissue-resident memory (Trm) CD8+ T cells mediate protective immunity in barrier tissues, but the cues promoting Trm cell 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 supported Trm cell generation by enhancing CD8+ T cell sensing of TGF-β, which was necessary for tissue residency. P2RX7-deficient Trm cells progressively decayed in non-lymphoid tissues and expressed dysregulated Trm-specific markers. P2RX7 was required for efficient re-expression of the receptor TGF-βRII through calcineurin signaling. Forced Tgfbr2 expression rescued P2RX7-deficient Trm cell generation, and TGF-β sensitivity was dictated by P2RX7 agonists and antagonists. Forced Tgfbr2 also rescued P2RX7-deficient Trm cell mitochondrial function. Sustained P2RX7 signaling was required for long-term Trm cell maintenance, indicating that P2RX7 signaling drives induction and CD8+ T cell durability in barrier sites. Borges da Silva et al. report that the extracellular ATP receptor P2RX7 promotes generation of virus-specific tissue-resident memory (Trm) CD8+T cells through induction of the TGF-β signaling pathway. Furthermore, long-term maintenance of Trm cells relies on continuous P2RX7 signaling.
登录
查看更多内容
DOI：
10.1084/jem.191.2.335
发表时间：
2000-01-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Daniels MA;Jameson SC
通讯作者：
Jameson SC
影响因子：
5.6
作者：
Dosch M;Gerber J;Jebbawi F;Beldi G
通讯作者：
Beldi G
影响因子：
4.4
作者：
Masopust, D;Vezys, V;Ahmed, R
通讯作者：
Ahmed, R
影响因子：
100.3
作者：
Farber, Donna L.;Netea, Mihai G.;Zinkernagel, Rolf M.
通讯作者：
Zinkernagel, Rolf M.
影响因子：
16.8
作者：
Iijima N;Iwasaki A
通讯作者：
Iwasaki A