Contribution of inhibitory receptor TIGIT to NK cell education
Contribution of inhibitory receptor TIGIT to NK cell education
复制标题
抑制性受体 TIGIT 对 NK 细胞教育的贡献
DOI：
10.1016/j.jaut.2017.04.001
复制
发表时间：
2017-07-01
影响因子：
12.8
通讯作者：
Tian, Zhigang
中科院分区：
文献类型：
--
作者：
He, Yuke;Peng, Hui;Tian, Zhigang
同源宿主MHC-I分子参与抑制受体触发NK细胞教育，导致功能成熟，并允许NK细胞感知缺失的自我。然而，NK细胞也表达非mhc - i配体的抑制受体，其在NM细胞教育中的作用尚不清楚。TIGIT是最近发现的一种抑制性受体，可识别非mhc - i配体CD155。在这里，我们证明了野生型小鼠的TIGIT(+) NM细胞对各种刺激表现出增强的反应性，包括缺乏CD155配体表达的靶标。然而，来自CD155缺陷宿主的TIGIT(+) NK细胞表现出功能损伤，表明宿主CD155与TIGIT受体的结合促进了NK细胞的功能成熟。此外，TIGIT缺陷以mhc -i不依赖和cd226不相关的方式损害NK细胞介导的CD155（-）靶点的自我识别缺失和排斥，如同种异体脾细胞和某些肿瘤细胞。因此，TIGIT-CD155通路也参与NK细胞最佳效应功能的获得，代表了一种新的不依赖mhc -i的NK细胞耐受和激活教育机制。(C) 2017年Elsevier Ltd.出版
Engagement of inhibitory receptors by cognate host MHC-I molecules triggers NK cell education, resulting in functional maturation and allowing NK cells to sense missing-self. However, NK cells also express inhibitory receptors for non-MHC-I ligands and their role in NM cell education is poorly understood. TIGIT is a recently identified inhibitory receptor that recognizes a non-MHC-I ligand CD155. Here, we demonstrated that TIGIT(+) NM cells from wild-type mice exerted augmented responsiveness to various stimuli, including targets that lacked expression of CD155 ligand. TIGIT(+) NK cells derived from CD155-deficient hosts, however, exhibited functional impairment, indicating that the engagement of TIGIT receptor by host CD155 promoted NK cell functional maturation. Furthermore, TIGIT deficiency impaired NK cell-mediated missing-self recognition and rejection of CD155(-) targets, such as allogenic splenocytes and certain tumor cells, in an MHC-I-independent and CD226-unrelated manner. Thus, TIGIT-CD155 pathway is also involved in the acquisition of optimal NK cell effector function, representing a novel MHC-I-independent education mechanism for NK cell tolerance and activation. (C) 2017 Published by Elsevier Ltd.