Cargando…

Critical roles of mTOR Complex 1 and 2 for T follicular helper cell differentiation and germinal center responses

T follicular helper (Tfh) cells play critical roles for germinal center responses and effective humoral immunity. We report here that mTOR in CD4 T cells is essential for Tfh differentiation. In Mtor(f/f)-Cd4Cre mice, both constitutive and inducible Tfh differentiation is severely impaired, leading...

Descripción completa

Detalles Bibliográficos
Autores principales: Yang, Jialong, Lin, Xingguang, Pan, Yun, Wang, Jinli, Chen, Pengcheng, Huang, Hongxiang, Xue, Hai-Hui, Gao, Jimin, Zhong, Xiao-Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063587/
https://www.ncbi.nlm.nih.gov/pubmed/27690224
http://dx.doi.org/10.7554/eLife.17936
_version_ 1782460006568820736
author Yang, Jialong
Lin, Xingguang
Pan, Yun
Wang, Jinli
Chen, Pengcheng
Huang, Hongxiang
Xue, Hai-Hui
Gao, Jimin
Zhong, Xiao-Ping
author_facet Yang, Jialong
Lin, Xingguang
Pan, Yun
Wang, Jinli
Chen, Pengcheng
Huang, Hongxiang
Xue, Hai-Hui
Gao, Jimin
Zhong, Xiao-Ping
author_sort Yang, Jialong
collection PubMed
description T follicular helper (Tfh) cells play critical roles for germinal center responses and effective humoral immunity. We report here that mTOR in CD4 T cells is essential for Tfh differentiation. In Mtor(f/f)-Cd4Cre mice, both constitutive and inducible Tfh differentiation is severely impaired, leading to defective germinal center B cell formation and antibody production. Moreover, both mTORC1 and mTORC2 contribute to Tfh and GC B cell development but may do so via distinct mechanisms. mTORC1 mainly promotes CD4 T cell proliferation to reach the cell divisions necessary for Tfh differentiation, while Rictor/mTORC2 regulates Tfh differentiation by promoting Akt activation and TCF1 expression without grossly influencing T cell proliferation. Together, our results reveal crucial but distinct roles for mTORC1 and mTORC2 in CD4 T cells during Tfh differentiation and germinal center responses. DOI: http://dx.doi.org/10.7554/eLife.17936.001
format Online
Article
Text
id pubmed-5063587
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher eLife Sciences Publications, Ltd
record_format MEDLINE/PubMed
spelling pubmed-50635872016-10-14 Critical roles of mTOR Complex 1 and 2 for T follicular helper cell differentiation and germinal center responses Yang, Jialong Lin, Xingguang Pan, Yun Wang, Jinli Chen, Pengcheng Huang, Hongxiang Xue, Hai-Hui Gao, Jimin Zhong, Xiao-Ping eLife Immunology T follicular helper (Tfh) cells play critical roles for germinal center responses and effective humoral immunity. We report here that mTOR in CD4 T cells is essential for Tfh differentiation. In Mtor(f/f)-Cd4Cre mice, both constitutive and inducible Tfh differentiation is severely impaired, leading to defective germinal center B cell formation and antibody production. Moreover, both mTORC1 and mTORC2 contribute to Tfh and GC B cell development but may do so via distinct mechanisms. mTORC1 mainly promotes CD4 T cell proliferation to reach the cell divisions necessary for Tfh differentiation, while Rictor/mTORC2 regulates Tfh differentiation by promoting Akt activation and TCF1 expression without grossly influencing T cell proliferation. Together, our results reveal crucial but distinct roles for mTORC1 and mTORC2 in CD4 T cells during Tfh differentiation and germinal center responses. DOI: http://dx.doi.org/10.7554/eLife.17936.001 eLife Sciences Publications, Ltd 2016-09-30 /pmc/articles/PMC5063587/ /pubmed/27690224 http://dx.doi.org/10.7554/eLife.17936 Text en © 2016, Yang et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Immunology
Yang, Jialong
Lin, Xingguang
Pan, Yun
Wang, Jinli
Chen, Pengcheng
Huang, Hongxiang
Xue, Hai-Hui
Gao, Jimin
Zhong, Xiao-Ping
Critical roles of mTOR Complex 1 and 2 for T follicular helper cell differentiation and germinal center responses
title Critical roles of mTOR Complex 1 and 2 for T follicular helper cell differentiation and germinal center responses
title_full Critical roles of mTOR Complex 1 and 2 for T follicular helper cell differentiation and germinal center responses
title_fullStr Critical roles of mTOR Complex 1 and 2 for T follicular helper cell differentiation and germinal center responses
title_full_unstemmed Critical roles of mTOR Complex 1 and 2 for T follicular helper cell differentiation and germinal center responses
title_short Critical roles of mTOR Complex 1 and 2 for T follicular helper cell differentiation and germinal center responses
title_sort critical roles of mtor complex 1 and 2 for t follicular helper cell differentiation and germinal center responses
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063587/
https://www.ncbi.nlm.nih.gov/pubmed/27690224
http://dx.doi.org/10.7554/eLife.17936
work_keys_str_mv AT yangjialong criticalrolesofmtorcomplex1and2fortfollicularhelpercelldifferentiationandgerminalcenterresponses
AT linxingguang criticalrolesofmtorcomplex1and2fortfollicularhelpercelldifferentiationandgerminalcenterresponses
AT panyun criticalrolesofmtorcomplex1and2fortfollicularhelpercelldifferentiationandgerminalcenterresponses
AT wangjinli criticalrolesofmtorcomplex1and2fortfollicularhelpercelldifferentiationandgerminalcenterresponses
AT chenpengcheng criticalrolesofmtorcomplex1and2fortfollicularhelpercelldifferentiationandgerminalcenterresponses
AT huanghongxiang criticalrolesofmtorcomplex1and2fortfollicularhelpercelldifferentiationandgerminalcenterresponses
AT xuehaihui criticalrolesofmtorcomplex1and2fortfollicularhelpercelldifferentiationandgerminalcenterresponses
AT gaojimin criticalrolesofmtorcomplex1and2fortfollicularhelpercelldifferentiationandgerminalcenterresponses
AT zhongxiaoping criticalrolesofmtorcomplex1and2fortfollicularhelpercelldifferentiationandgerminalcenterresponses