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

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 n...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107092/
https://www.ncbi.nlm.nih.gov/pubmed/33733611
http://dx.doi.org/10.1111/jcmm.16465
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author 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
author_facet 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
author_sort Lei, Lei
collection PubMed
description 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.
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spelling pubmed-81070922021-05-10 Med1 controls CD8 T cell maintenance through IL‐7R‐mediated cell survival signalling 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 J Cell Mol Med Original Articles 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. John Wiley and Sons Inc. 2021-03-17 2021-05 /pmc/articles/PMC8107092/ /pubmed/33733611 http://dx.doi.org/10.1111/jcmm.16465 Text en © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
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
Med1 controls CD8 T cell maintenance through IL‐7R‐mediated cell survival signalling
title Med1 controls CD8 T cell maintenance through IL‐7R‐mediated cell survival signalling
title_full Med1 controls CD8 T cell maintenance through IL‐7R‐mediated cell survival signalling
title_fullStr Med1 controls CD8 T cell maintenance through IL‐7R‐mediated cell survival signalling
title_full_unstemmed Med1 controls CD8 T cell maintenance through IL‐7R‐mediated cell survival signalling
title_short Med1 controls CD8 T cell maintenance through IL‐7R‐mediated cell survival signalling
title_sort med1 controls cd8 t cell maintenance through il‐7r‐mediated cell survival signalling
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107092/
https://www.ncbi.nlm.nih.gov/pubmed/33733611
http://dx.doi.org/10.1111/jcmm.16465
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