Stress hormone signalling inhibits Th1 polarization in a CD4 T-cell-intrinsic manner via mTORC1 and the circadian gene PER1

Christophe M. Capelle, Anna Chen, Ni Zeng, Alexandre Baron, Kamil Grzyb, Thais Arns, Alexander Skupin, Markus Ollert, Feng Q. Hefeng*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

5 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)428-444
Number of pages17
JournalImmunology
Volume165
Issue number4
Early online date10 Feb 2022
DOIs
Publication statusPublished - Apr 2022

Keywords

  • adrenergic signalling
  • circadian rhythm
  • neuroimmunology
  • PER1
  • stress
  • T-cell differentiation

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