Peter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, UK.
Peter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, UK; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford OX3 9DU, UK.
Cell Rep. 2019 Sep 17;28(12):3077-3091.e5. doi: 10.1016/j.celrep.2019.08.050.
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 tissue-repair 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.
MAIT 细胞是一种非常规的 T 细胞群体，可通过 TCR 依赖和 TCR 非依赖机制激活。在这里，我们研究了 TCR 依赖和 TCR 非依赖信号组合对人 CD8 MAIT 细胞的影响。通过扩展细胞因子谱，包括 TNF 超家族成员 TL1A，从血液和肠道中最大程度地激活这些 MAIT 细胞的 TCR 非依赖性激活。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 TCR 触发本身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。总之，这些数据表明，CD8 MAIT 细胞中 TCR 依赖和 TCR 非依赖信号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。
