TCR and Inflammatory Signals Tune Human MAIT Cells to Exert Specific Tissue Repair and Effector Functions
TCR and Inflammatory Signals Tune Human MAIT Cells to Exert Specific Tissue Repair and Effector Functions
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DOI：
10.1016/j.celrep.2019.08.050
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发表时间：
2019-09-17
期刊：
影响因子：
8.8
通讯作者：
Uhlig, Holm H.
中科院分区：
文献类型：
--
作者：
Leng, Tianqi;Akther, Hossain Delowar;Uhlig, Holm H.
MAIT 细胞是一种非常规 T 细胞群，可以通过 TCR 依赖性和 TCR 独立机制激活。在这里，我们研究了 TCR 依赖性和 TCR 独立信号组合对人 CD8(+) MAIT 细胞的影响。通过扩展细胞因子组以包括 TNF 超家族成员 TL1A，可以最大限度地提高血液和肠道中这些 MAIT 细胞的 TCR 依赖性激活。 RNA-seq实验表明，TCR依赖性和TCR非依赖性信号驱动MAIT细胞发挥重叠和特定的效应功能，影响宿主防御和组织稳态。尽管仅 TCR 触发不足以驱动持续激活，但 TCR 触发的 MAIT 细胞在基因和蛋白质水平以及体外测定中显示出组织修复功能的特异性富集。总而言之，这些数据表明，CD8(+) MAIT细胞的TCR依赖性和TCR非依赖性信号传导的混合可能在控制组织炎症和修复的健康和病理过程之间的平衡中发挥作用。
MAIT cells are an unconventional T cell population that can be activated through both TCR-dependent and TCR-independent mechanisms. Here, we examined the impact of combinations of TCR-dependent and TCR-independent signals in human CD8(+) MAIT cells. TCR-independent activation of these MAIT cells from blood and gut was maximized by extending the panel of cytokines to include TNF-superfamily member TL1A. RNA-seq experiments revealed that TCR-dependent and TCR-independent signals drive MAIT cells to exert overlapping and specific effector functions, affecting both host defense and tissue homeostasis. Although TCR triggering alone is insufficient to drive sustained activation, TCR-triggered MAIT cells showed specific enrichment of tissuerepair functions at the gene and protein levels and in in vitro assays. Altogether, these data indicate the blend of TCR-dependent and TCR-independent signaling to CD8(+) MAIT cells may play a role in controlling the balance between healthy and pathological processes of tissue inflammation and repair.