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We and others have previously shown that Sema4A and H\u2010ferritin interact through the T\u2010cell immunoglobulin and mucin domain (Tim\u20102) receptor in mice. H\u2010ferritin has been identified as the iron delivery protein for oligodendrocytes, whereas Sema4A causes a direct cytotoxic effect. However, the expression of Tim\u20102 has not been detected in humans. Here, we demonstrate that, similar to rodents, human oligodendrocytes undergo apoptosis when exposed to Sema4A and take up H\u2010ferritin for meeting iron requirements and that these functions are mediated via the Tim\u20101 receptor. Moreover, we also demonstrate the ability of H\u2010ferritin to block Sema4A\u2010mediated cytotoxicity. Furthermore, we show in a series of pilot studies that Sema4A is detectable in the CSF of multiple sclerosis patients and HIV\u2010seropositive persons and can induce oligodendrocyte cell death. Together, these results identify a novel iron uptake mechanism for human oligodendrocytes and a connection between oligodendrocytes and the immune system.<\/jats:p>","DOI":"10.1002\/glia.23313","type":"journal-article","created":{"date-parts":[[2018,2,23]],"date-time":"2018-02-23T16:01:20Z","timestamp":1519401680000},"page":"1317-1330","source":"Crossref","is-referenced-by-count":67,"title":["Semaphorin4A and H\u2010ferritin utilize Tim\u20101 on human oligodendrocytes: A novel neuro\u2010immune axis"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6322-1914","authenticated-orcid":false,"given":"Brian","family":"Chiou","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Penn State University College of Medicine Hershey Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Lucassen","sequence":"additional","affiliation":[{"name":"Department of Neurology Penn State University College of Medicine Hershey Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Sather","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Penn State University College of Medicine Hershey Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asha","family":"Kallianpur","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine Cleveland Clinic\/Lerner Research Institute Cleveland Ohio"},{"name":"Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine Case Western Reserve University Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Connor","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Penn State University College of Medicine Hershey Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,2,19]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M200562200"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2003483"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1027324230923"},{"key":"e_1_2_7_5_1","first-page":"1","article-title":"Semaphorins 4A and 4D in chronic inflammatory diseases","author":"Chapoval S. 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