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As the blood\u2212brain barrier is the immunological interface between the brain and the periphery, we investigated whether this vascular phenotype is intrinsically compromised in the most common genetic risk factor for schizophrenia, the 22q11.2 deletion syndrome (22qDS). Blood\u2212brain barrier like endothelium differentiated from human 22qDS+schizophrenia-induced pluripotent stem cells exhibited impaired barrier integrity, a phenotype substantiated in a mouse model of 22qDS. The proinflammatory intercellular adhesion molecule-1 was upregulated in 22qDS+schizophrenia-induced blood\u2013brain barrier and in 22qDS mice, indicating compromise of the blood\u2013brain barrier immune privilege. This immune imbalance resulted in increased migration\/activation of leucocytes crossing the 22qDS+schizophrenia blood\u2212brain barrier. We also found heightened astrocyte activation in murine 22qDS, suggesting that the blood\u2212brain barrier promotes astrocyte-mediated neuroinflammation. Finally, we substantiated these findings in post-mortem 22qDS brain tissue. Overall, the barrier-promoting and immune privilege properties of the 22qDS blood\u2013brain barrier are compromised, and this might increase the risk for neuropsychiatric disease.<\/jats:p>","DOI":"10.1093\/brain\/awab055","type":"journal-article","created":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T23:16:31Z","timestamp":1614726991000},"page":"1351-1360","source":"Crossref","is-referenced-by-count":70,"title":["Disruption of the blood\u2013brain barrier in 22q11.2 deletion syndrome"],"prefix":"10.1093","volume":"144","author":[{"given":"Alexis M","family":"Crockett","sequence":"first","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean K","family":"Ryan","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry, Children\u2019s Hospital of Philadelphia, Philadelphia, PA 19104, 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