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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

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

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).

OriginalsprogEngelsk
TidsskriftThe Journal of Experimental Medicine
Vol/bind216
Udgave nummer3
Sider (fra-til)517-526
Antal sider10
ISSN0022-1007
DOI
StatusUdgivet - 2019

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