Med1 controls CD8 T cell maintenance through IL-7R-mediated cell survival signalling.

Journal of cellular and molecular medicine 2021 May

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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. © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Citation

Lei Lei, Xiaofeng Yang, Yanhong Su, Huiqiang Zheng, Jun Liu, Haiyan Liu, Yujing Zou, Anjun Jiao, Xin Wang, Cangang Zhang, Xingzhe Zhang, Jiahui Zhang, Dan Zhang, Xiaobo Zhou, Lin Shi, Enqi Liu, Liang Bai, Chenming Sun, Baojun Zhang. Med1 controls CD8 T cell maintenance through IL-7R-mediated cell survival signalling. Journal of cellular and molecular medicine. 2021 May;25(10):4870-4876