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

Stoyan Dimitrov; Tanja Lange; Cécile Gouttefangeas; Anja T R Jensen; Michael Szczepanski; Jannik Lehnnolz; Surjo Soekadar; Hans-Georg Rammensee; Jan Born; Luciana Besedovsky

doi:10.1084/jem.20181169

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

Stoyan Dimitrov, Tanja Lange, Cécile Gouttefangeas, Anja T R Jensen, Michael Szczepanski, Jannik Lehnnolz, Surjo Soekadar, Hans-Georg Rammensee, Jan Born, Luciana Besedovsky

TARGETS team

17 Citations (Scopus)

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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).

Original language	English
Journal	The Journal of Experimental Medicine
Volume	216
Issue number	3
Pages (from-to)	517-526
Number of pages	10
ISSN	0022-1007
DOIs	https://doi.org/10.1084/jem.20181169
Publication status	Published - 1 Mar 2019

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Gαs-coupled receptor signaling and sleep regulate integrin activation of human antigen-specific T cellsFinal published version, 1.64 MBLicence: CC BY-NC-SA

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title = "Gαs-coupled receptor signaling and sleep regulate integrin activation of human antigen-specific T cells",

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).",

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T1 - Gαs-coupled receptor signaling and sleep regulate integrin activation of human antigen-specific T cells

AU - Dimitrov, Stoyan

AU - Lange, Tanja

AU - Gouttefangeas, Cécile

AU - Jensen, Anja T R

AU - Szczepanski, Michael

AU - Lehnnolz, Jannik

AU - Soekadar, Surjo

AU - Rammensee, Hans-Georg

AU - Born, Jan

AU - Besedovsky, Luciana

PY - 2019/3/1

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N2 - 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).

AB - 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).

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DO - 10.1084/jem.20181169

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SN - 0022-1007

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EP - 526

JO - The Journal of Experimental Medicine

JF - The Journal of Experimental Medicine

IS - 3

ER -

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

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