@article{75bb9d17d76f46dc87ce553875a90c97,
title = "Stress hormone signalling inhibits Th1 polarization in a CD4 T-cell-intrinsic manner via mTORC1 and the circadian gene PER1",
abstract = "Stress hormones are believed to skew the CD4 T-cell differentiation towards a Th2 response via a T-cell-extrinsic mechanism. Using isolated primary human na{\"i}ve and memory CD4 T cells, here we show that both adrenergic- and glucocorticoid-mediated stress signalling pathways play a CD4 na{\"i}ve T-cell-intrinsic role in regulating the Th1/Th2 differentiation balance. Both stress hormones reduced the Th1 programme and cytokine production by inhibiting mTORC1 signalling via two parallel mechanisms. Stress hormone signalling inhibited mTORC1 in na{\"i}ve CD4 T cells (1) by affecting the PI3K/AKT pathway and (2) by regulating the expression of the circadian rhythm gene, period circadian regulator 1 (PER1). Both stress hormones induced the expression of PER1, which inhibited mTORC1 signalling, thus reducing Th1 differentiation. This previously unrecognized cell-autonomous mechanism connects stress hormone signalling with CD4 T-cell differentiation via mTORC1 and a specific circadian clock gene, namely PER1.",
keywords = "adrenergic signalling, circadian rhythm, neuroimmunology, PER1, stress, T-cell differentiation",
author = "Capelle, {Christophe M.} and Anna Chen and Ni Zeng and Alexandre Baron and Kamil Grzyb and Thais Arns and Alexander Skupin and Markus Ollert and Hefeng, {Feng Q.}",
note = "Funding Information: We particularly appreciate anonymous donors and Luxembourg Red Cross for providing buffy coats to us. The Hefeng group was supported by Luxembourg National Research Fund (FNR) through different programmes including AFR‐RIKEN bilateral programme (TregBAR, 11228353), PRIDE/2015/10907093/CRITICS to support C.C., individual Aide {\`a} la Formation Recherche (AFR) grant PHD‐2015‐1/9989160 to support N.Z. and intramural funding within Luxembourg Institute of Health and Luxembourg Centre for Systems Biomedicine, from Minist{\`e}re de l'Enseignement sup{\'e}rieur et de la Recherche (MESR). M.O. was supported as co‐ordinator by the Luxembourg National Research Fund (FNR) through the FNR PRIDE programme for doctoral training unit (PRIDE/11012546/NEXTIMMUNE). Some icons in schematic Figure 1 and the graphical summary/abstract were created from BioRender.com. Publisher Copyright: {\textcopyright} 2022 The Authors. Immunology published by John Wiley & Sons Ltd.",
year = "2022",
month = apr,
doi = "10.1111/imm.13448",
language = "English",
volume = "165",
pages = "428--444",
journal = "Immunology",
issn = "0019-2805",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "4",
}