Med1通过IL-7R介导的细胞存活信号通路控制CD8 T细胞的维持。
Med1 controls CD8 T cell maintenance through IL-7R-mediated cell survival signalling.
作者信息
Lei Lei, Yang Xiaofeng, Su Yanhong, Zheng Huiqiang, Liu Jun, Liu Haiyan, Zou Yujing, Jiao Anjun, Wang Xin, Zhang Cangang, Zhang Xingzhe, Zhang Jiahui, Zhang Dan, Zhou Xiaobo, Shi Lin, Liu Enqi, Bai Liang, Sun Chenming, Zhang Baojun
机构信息
Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, China.
Institute of Infection and Immunity, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an, China.
出版信息
J Cell Mol Med. 2021 May;25(10):4870-4876. doi: 10.1111/jcmm.16465. Epub 2021 Mar 17.
Under steady-state conditions, the pool size of peripheral CD8 T cells is maintained through turnover and survival. Beyond TCR and IL-7R signals, the underlying mechanisms are less well understood. In the present study, we found a significant reduction of CD8 T cell proportion in spleens but not in thymi of mice with T cell-specific deletion of Mediator Subunit 1 (Med1). A competitive transfer of wild-type (WT) and Med1-deficient CD8 T cells reproduced the phenotype in the same recipients and confirmed intrinsic role of Med1. Furthermore, we observed a comparable degree of migration and proliferation but a significant increase of cell death in Med1-deficient CD8 T cells compared with WT counterparts. Finally, Med1-deficient CD8 T cells exhibited a decreased expression of interleukin-7 receptor α (IL-7Rα), down-regulation of phosphorylated-STAT5 (pSTAT5) and Bim up-regulation. Collectively, our study reveals a novel role of Med1 in the maintenance of CD8 T cells through IL-7Rα/STAT5 pathway-mediated cell survival.
在稳态条件下，外周CD8 T细胞库的大小通过细胞更新和存活得以维持。除了TCR和IL-7R信号外，其潜在机制尚不清楚。在本研究中，我们发现Mediator亚基1（Med1）T细胞特异性缺失的小鼠脾脏中CD8 T细胞比例显著降低，但胸腺中未出现这种情况。野生型（WT）和Med1缺陷型CD8 T细胞的竞争性转移在相同受体中重现了该表型，并证实了Med1的内在作用。此外，与WT CD8 T细胞相比，我们观察到Med1缺陷型CD8 T细胞的迁移和增殖程度相当，但细胞死亡显著增加。最后，Med1缺陷型CD8 T细胞表现出白细胞介素-7受体α（IL-7Rα）表达降低、磷酸化STAT5（pSTAT5）下调和Bim上调。总之，我们的研究揭示了Med1通过IL-7Rα/STAT5途径介导的细胞存活在维持CD8 T细胞中的新作用。
Zotero 插件