TY - JOUR T1 - Disruption of the Blood-Brain Barrier in 22q11.2 Deletion Syndrome JF - bioRxiv DO - 10.1101/824987 SP - 824987 AU - Alexis M. Crockett AU - Sean K. Ryan AU - Adriana Hernandez Vasquez AU - Caroline Canning AU - Nickole Kanyuch AU - Hania Kebir AU - Guadalupe Ceja AU - James Gesualdi AU - Angela Viaene AU - Richa Kapoor AU - Naïl Benallegue AU - Stewart A. Anderson AU - Jorge I. Alvarez Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/11/14/824987.abstract N2 - Neuroimmune dysregulation is implicated in neuropsychiatric disorders including schizophrenia (SZ). As the blood brain barrier (BBB) is the immunological interface between the brain and the periphery, we investigated whether the BBB is intrinsically compromised in the most common genetic risk factor for SZ, the hemizygous deletion of chromosome 22q11.2 (22qDS). BBB-like endothelium (iBBB) differentiated from human 22qDS+SZ-induced pluripotent stem cells exhibited impaired barrier integrity, a phenotype substantiated in a mouse model of 22qDS. The proinflammatory intercellular adhesion molecule-1 (ICAM-1) was upregulated in 22qDS+SZ iBBB and 22qDS mice, indicating compromise of the BBB immune privilege. This immune imbalance resulted in increased migration/activation of leukocytes crossing the 22qDS+SZ iBBB. Finally, we found heightened astrocyte activation in murine and human 22qDS, suggesting that the BBB promotes astrocyte-mediated neuroinflammation. Overall, the barrier-promoting and immune privilege properties of the 22qDS BBB are compromised, and this might increase the risk for neuropsychiatric disease. ER -