{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T07:09:54Z","timestamp":1790233794097,"version":"4.1.0"},"reference-count":54,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2023,6,20]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Typically defined as a thromboinflammatory disease, ischemic stroke features early and delayed inflammatory responses, which determine the extent of ischemia\u2010related brain damage. T and natural killer cells have been implicated in neuronal cytotoxicity and inflammation, but the precise mechanisms of immune cell\u2010mediated stroke progression remain poorly understood. The activating immunoreceptor NKG2D is expressed on both natural killer and T cells and may be critically involved.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              An anti\u2010NKG2D blocking antibody alleviated stroke outcome in terms of infarct volume and functional deficits, coinciding with reduced immune cell infiltration into the brain and improved survival in the animal model of cerebral ischemia. Using transgenic knockout models devoid of certain immune cell types and immunodeficient mice supplemented with different immune cell subsets, we dissected the functional contribution of NKG2D signaling by different NKG2D\u2010expressing cells in stroke pathophysiology. The observed effect of NKG2D signaling in stroke progression was shown to be predominantly mediated by natural killer and CD8\n              <jats:sup>+<\/jats:sup>\n              T cells. Transfer of T cells with monovariant T\u2010cell receptors into immunodeficient mice with and without pharmacological blockade of NKG2D revealed activation of CD8\n              <jats:sup>+<\/jats:sup>\n              T cells irrespective of antigen specificity. Detection of the NKG2D receptor and its ligands in brain samples of patients with stroke strengthens the relevance of preclinical observations in human disease.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Our findings provide a mechanistic insight into NKG2D\u2010dependent natural killer\u2013 and T\u2010cell\u2013mediated effects in stroke pathophysiology.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.122.029529","type":"journal-article","created":{"date-parts":[[2023,6,11]],"date-time":"2023-06-11T02:22:50Z","timestamp":1686450170000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["Impact of NKG2D Signaling on Natural Killer and T\u2010Cell Function in Cerebral Ischemia"],"prefix":"10.1161","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5487-9979","authenticated-orcid":false,"given":"Christina","family":"David","sequence":"first","affiliation":[{"name":"Department of Neurology With Center for Translational Neuro\u2010 and Behavioral Sciences (C\u2010TNBS) University Hospital Essen, University Duisburg\u2010Essen Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6332-8650","authenticated-orcid":false,"given":"Tobias","family":"Ruck","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty Heinrich\u2010Heine\u2010University D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leoni","family":"Rolfes","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty Heinrich\u2010Heine\u2010University D\u00fcsseldorf 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