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To dissect the mechanisms underlying PHE formation, we profiled human and mouse perihematomal tissues and identified natural killer (NK) cells as the predominant immune cell subset that outnumbers other infiltrating immune cell types during early stages of ICH. Unbiased clustering of single-cell transcriptional profiles revealed two major NK cell subsets that respectively possess high cytotoxicity or robust chemokine production features in the brain after ICH, distinguishing them from NK cells of the periphery. NK cells exacerbate BBB disruption and brain edema after ICH via cytotoxicity toward cerebral endothelial cells and recruitment of neutrophils that augment focal inflammation. Thus, brain-bound NK cells acquire new features that contribute to PHE formation and neurological deterioration following ICH.<\/jats:p>","DOI":"10.1084\/jem.20200213","type":"journal-article","created":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T13:20:32Z","timestamp":1598966432000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":137,"title":["Brain transforms natural killer cells that exacerbate brain edema after intracerebral hemorrhage"],"prefix":"10.1084","volume":"217","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6869-2766","authenticated-orcid":true,"given":"Zhiguo","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China 1"},{"name":"National Clinical Research Center for Neurological Disease of China, Jing-Jin Center for Neuroinflammation, Beijing Tiantan Hospital, Capital Medical University, Beijing, China 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8209-4095","authenticated-orcid":true,"given":"Minshu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China 1"},{"name":"National Clinical Research Center for Neurological Disease of China, Jing-Jin Center for Neuroinflammation, Beijing Tiantan Hospital, Capital Medical University, Beijing, China 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2773-1826","authenticated-orcid":true,"given":"Samuel X.","family":"Shi","sequence":"additional","affiliation":[{"name":"Interdisciplinary Neuroscience Graduate Program, Arizona State University, Tempe, AZ 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8884-7852","authenticated-orcid":true,"given":"Nan","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5491-3540","authenticated-orcid":true,"given":"Xiaojing","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2658-0106","authenticated-orcid":true,"given":"Ai","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6955-0903","authenticated-orcid":true,"given":"Zilong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tianjin Huanhu Hospital, Tianjin, China 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7003-4543","authenticated-orcid":true,"given":"Xiaoan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6621-0591","authenticated-orcid":true,"given":"Qiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2020,9,1]]},"reference":[{"key":"2023072801161712700_bib1","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/nrneurol.2010.76","article-title":"Fingolimod is a potential novel therapy for multiple sclerosis","volume":"6","author":"Aktas","year":"2010","journal-title":"Nat. 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