Reference : Stress hormone signalling inhibits Th1 polarization in a CD4 T-cell-intrinsic manner ...
Scientific journals : Article
Human health sciences : Immunology & infectious disease
http://hdl.handle.net/10993/51827
Stress hormone signalling inhibits Th1 polarization in a CD4 T-cell-intrinsic manner via mTORC1 and the circadian gene PER1
English
Capelle, Christophe M. [> >]
Chen, Anna [> >]
Zeng, Ni [> >]
Baron, Alexandre [> >]
Grzyb, Kamil mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Integrative Cell Signalling]
Arns, Thais mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Integrative Cell Signalling]
Skupin, Alexander mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Integrative Cell Signalling]
Ollert, Markus mailto [University of Luxembourg > >]
He, Feng mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) >]
2022
Immunology
Blackwell
165
4
428--444
Yes
0019-2805
1365-2567
Oxford
United Kingdom
[en] adrenergic signalling ; circadian rhythm ; neuroimmunology ; PER1 ; stress ; T-cell differentiation
[en] 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 naïve and memory CD4 T cells, here we show that both adrenergic- and glucocorticoid-mediated stress signalling pathways play a CD4 naïve 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 naïve 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.
http://hdl.handle.net/10993/51827
10.1111/imm.13448
https://onlinelibrary.wiley.com/doi/abs/10.1111/imm.13448
\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/imm.13448

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