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Vascular pathology is an important factor for the development and progression of CNS pathology of MS, yet the role of ADMA in MS remains elusive. Patients with multiple sclerosis (MS) are reported to have elevated blood levels of ADMA, and mice with experimental autoimmune encephalomyelitis (EAE, an animal model of MS) generated by auto\u2010immunization of myelin oligodendrocyte glycoprotein (MOG) and blood\u2013brain barrier (BBB) disruption by pertussis toxin also had increased blood ADMA levels in parallel with induction of clinical disease. To explore the role of ADMA in EAE pathogenesis, EAE mice were treated with a daily dose of ADMA. It is of special interest that ADMA treatment enhanced the BBB disruption in EAE mice and exacerbated the clinical and CNS disease of EAE. ADMA treatment also induced the BBB disruption and EAE disease in MOG\u2010immunized mice even without pertussis toxin treatment, suggesting the role of ADMA in BBB dysfunction in EAE. T\u2010cell polarization studies also documented that ADMA treatment promotes T<jats:sub>H<\/jats:sub>1\u2010 and T<jats:sub>H<\/jats:sub>17\u2010mediated immune responses but without affecting Treg\u2010mediated immune response in EAE mice as well as in in vitro T\u2010cell culture. Taken together, these data, for the first time, document the vascular and immunopathogenic roles of ADMA in EAE, thus pointing to the potential of ADMA\u2010mediated mechanism as a new target of potential therapy for MS.<\/jats:p>","DOI":"10.1111\/imm.13396","type":"journal-article","created":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T12:59:21Z","timestamp":1627304361000},"page":"602-616","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Vascular and immunopathological role of Asymmetric Dimethylarginine (ADMA) in Experimental Autoimmune Encephalomyelitis"],"prefix":"10.1111","volume":"164","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1013-5569","authenticated-orcid":false,"given":"Inderjit","family":"Singh","sequence":"first","affiliation":[{"name":"Department of Pediatrics Medical University of South Carolina Charleston South Carolina USA"},{"name":"Research Service Ralph H. 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