Stress hormone signalling inhibits Th1 polarization in a CD4 T-cell-intrinsic manner via mTORC1 and the circadian gene PER1
| Autor: | Christophe M. Capelle, Anna Chen, Ni Zeng, Alexandre Baron, Kamil Grzyb, Thais Arns, Alexander Skupin, Markus Ollert, Feng Q. Hefeng |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
CD4-Positive T-Lymphocytes
circadian rhythm Immunology Medizin Cell Differentiation T-cell differentiation Period Circadian Proteins PER1 Mechanistic Target of Rapamycin Complex 1 Th1 Cells neuroimmunology Hormones Phosphatidylinositol 3-Kinases stress Th2 Cells Humans Immunology and Allergy adrenergic signalling |
| Zdroj: | Capelle, C M, Chen, A, Zeng, N, Baron, A, Grzyb, K, Arns, T, Skupin, A, Ollert, M & Hefeng, F Q 2022, ' Stress hormone signalling inhibits Th1 polarization in a CD4 T-cell-intrinsic manner via mTORC1 and the circadian gene PER1 ', Immunology, vol. 165, no. 4, pp. 428-444 . https://doi.org/10.1111/imm.13448 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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