{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:09:17Z","timestamp":1787166557820,"version":"build-2736575974"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T00:00:00Z","timestamp":1661385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971110"],"award-info":[{"award-number":["81971110"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Guangzhou Science and Technology Program Key Project","award":["202007030010"],"award-info":[{"award-number":["202007030010"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101450"],"award-info":[{"award-number":["82101450"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Natural killer (NK) cells are enriched in the central nervous system in aging-related atheriosclerotic cerebral small vessel disease (aCSVD), but their roles and underlying mechanism remain to be elucidated. To identify potential cytotoxic molecules released by NK cells in aCSVD lesions, proteomic analysis of cerebrospinal fluid (CSF), plasma, and peripheral NK cells from patients with aCSVD were performed. We found that integrin \u03b22 (ITGB2), cathepsin D (CTSD), and granzyme H (GZMH) were highly expressed in NK cells. ITGB2 interacted with intercellular adhesion molecule 1 in vascular endothelial cells. As assessed by immunofluorescence and scanning electron microscopy of the blood\u2013brain barrier model, transwell membranes covered with primary human brain microvascular endothelial cells and astrocytes, we demonstrated that the CTSD-mediated degradation of collagen in the blood\u2013brain barrier depended on the cytotoxicity of NK cells in aCSVD. With the immunostaining in vitro and in vivo, GZMH disruption of demyelinated nerve fibers was reversed by cotreatment with the inhibitor 3,4-DCIC during white matter hyperintensity (WMH) in aCSVD. Our results indicate that NK cells contribute to CTSD-induced damage to the blood\u2013brain barrier and GZMH-induced disruption of nerve fibers during WMH in aCSVD.<\/jats:p>","DOI":"10.1093\/gerona\/glac173","type":"journal-article","created":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T12:28:01Z","timestamp":1661430481000},"page":"414-423","source":"Crossref","is-referenced-by-count":13,"title":["Natural Killer Cells Disrupt Nerve Fibers by Granzyme H in Atheriosclerotic Cerebral Small Vessel Disease"],"prefix":"10.1093","volume":"78","author":[{"given":"Dafan","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Neurology, Mental and Neurological Disease Research Center, the Third Affiliated Hospital of Sun Yat-sen University , Guangzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mental and Neurological Disease Research Center, the 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