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J Exp Med. 2019 Mar 4;216(3):517-526. doi: 10.1084/jem.20181169. Epub 2019 Feb 12.

s-coupled receptor signaling and sleep regulate integrin activation of human antigen-specific T cells.

Author information

1
Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen, Tübingen, Germany stoyan.dimitrov@uni-tuebingen.de.
2
German Center for Diabetes Research (DZD), Tübingen, Germany.
3
Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich, University of Tübingen, Tübingen, Germany.
4
Clinic for Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany.
5
Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany.
6
Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
7
Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen, Tübingen, Germany.
8
Clinical Neurotechnology Laboratory, Department of Psychiatry and Psychotherapy, Neuroscience Research Center, Charité - University Medicine Berlin, Berlin, Germany.
9
Partner Site Tübingen, German Cancer Consortium, Tübingen, Germany.

Abstract

Efficient T cell responses require the firm adhesion of T cells to their targets, e.g., virus-infected cells, which depends on T cell receptor (TCR)-mediated activation of β2-integrins. Gαs-coupled receptor agonists are known to have immunosuppressive effects, but their impact on TCR-mediated integrin activation is unknown. Using multimers of peptide major histocompatibility complex molecules (pMHC) and of ICAM-1-the ligand of β2-integrins-we show that the Gαs-coupled receptor agonists isoproterenol, epinephrine, norepinephrine, prostaglandin (PG) E2, PGD2, and adenosine strongly inhibit integrin activation on human CMV- and EBV-specific CD8+ T cells in a dose-dependent manner. In contrast, sleep, a natural condition of low levels of Gαs-coupled receptor agonists, up-regulates integrin activation compared with nocturnal wakefulness, a mechanism possibly underlying some of the immune-supportive effects of sleep. The findings are also relevant for several pathologies associated with increased levels of Gαs-coupled receptor agonists (e.g., tumor growth, malaria, hypoxia, stress, and sleep disturbances).

PMID:
30755455
PMCID:
PMC6400544
[Available on 2019-09-04]
DOI:
10.1084/jem.20181169

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