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G\u03b1s-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\u2014the ligand of \u03b22-integrins\u2014we show that the G\u03b1s-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 G\u03b1s-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 G\u03b1s-coupled receptor agonists (e.g., tumor growth, malaria, hypoxia, stress, and sleep disturbances).<\/jats:p>","DOI":"10.1084\/jem.20181169","type":"journal-article","created":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T19:36:24Z","timestamp":1550000184000},"page":"517-526","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":56,"title":["G\u03b1s-coupled receptor signaling and sleep regulate integrin activation of human antigen-specific T cells"],"prefix":"10.1084","volume":"216","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1184-1441","authenticated-orcid":true,"given":"Stoyan","family":"Dimitrov","sequence":"first","affiliation":[{"name":"Institute of Medical Psychology and Behavioral Neurobiology, University of T\u00fcbingen, T\u00fcbingen, Germany 1"},{"name":"German Center for Diabetes Research (DZD), T\u00fcbingen, Germany 2"},{"name":"Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich, University of T\u00fcbingen, T\u00fcbingen, Germany 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8309-2112","authenticated-orcid":true,"given":"Tanja","family":"Lange","sequence":"additional","affiliation":[{"name":"Clinic for Rheumatology and Clinical Immunology, University of L\u00fcbeck, L\u00fcbeck, Germany 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Gouttefangeas","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute for Cell Biology, University of T\u00fcbingen, T\u00fcbingen, Germany 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja T.R.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Szczepanski","sequence":"additional","affiliation":[{"name":"Institute of Medical Psychology and Behavioral Neurobiology, University of T\u00fcbingen, T\u00fcbingen, Germany 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jannik","family":"Lehnnolz","sequence":"additional","affiliation":[{"name":"Institute of Medical Psychology and Behavioral Neurobiology, University of T\u00fcbingen, T\u00fcbingen, Germany 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1280-5538","authenticated-orcid":false,"given":"Surjo","family":"Soekadar","sequence":"additional","affiliation":[{"name":"Institute of Medical Psychology and Behavioral Neurobiology, University of T\u00fcbingen, T\u00fcbingen, Germany 1"},{"name":"Clinical Neurotechnology Laboratory, Department of Psychiatry and Psychotherapy, Neuroscience Research Center, Charite\u0301 \u2013 University Medicine Berlin, Berlin, Germany 7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1614-2647","authenticated-orcid":true,"given":"Hans-Georg","family":"Rammensee","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute for Cell Biology, University of T\u00fcbingen, T\u00fcbingen, Germany 5"},{"name":"Partner Site T\u00fcbingen, German Cancer Consortium, T\u00fcbingen, Germany 8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1847-6248","authenticated-orcid":false,"given":"Jan","family":"Born","sequence":"additional","affiliation":[{"name":"Institute of Medical Psychology and Behavioral Neurobiology, University of T\u00fcbingen, T\u00fcbingen, Germany 1"},{"name":"German Center for Diabetes Research (DZD), T\u00fcbingen, Germany 2"},{"name":"Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich, University of T\u00fcbingen, T\u00fcbingen, Germany 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana","family":"Besedovsky","sequence":"additional","affiliation":[{"name":"Institute of Medical Psychology and Behavioral Neurobiology, University of T\u00fcbingen, T\u00fcbingen, Germany 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2019,2,12]]},"reference":[{"key":"2023072604361079400_bib1","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1146\/annurev.immunol.021908.132554","article-title":"The ins and outs of leukocyte integrin signaling","volume":"27","author":"Abram","year":"2009","journal-title":"Annu. 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