{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T19:58:50Z","timestamp":1779134330179,"version":"3.51.4"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,4,16]],"date-time":"2018-04-16T00:00:00Z","timestamp":1523836800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007496","name":"Biomedical Laboratory Research and Development, VA Office of Research and Development","doi-asserted-by":"publisher","award":["I01BX007080"],"award-info":[{"award-number":["I01BX007080"]}],"id":[{"id":"10.13039\/100007496","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2018,9]]},"abstract":"Summary<\/jats:title>In the past there have been a multitude of studies that ardently support the role of arginase II<\/jats:styled-content> (Arg II<\/jats:styled-content>) in vascular and endothelial disorders; however, the regulation and function of Arg II<\/jats:styled-content> in autoimmune diseases has thus far remained unclear. Here we report that a global Arg II<\/jats:styled-content> null mutation in mice suppressed experimental autoimmune encephalomyelitis (EAE<\/jats:styled-content>), an animal model of multiple sclerosis. During EAE<\/jats:styled-content>, both Arg I and Arg II<\/jats:styled-content> were induced in spinal cords, but only Arg II<\/jats:styled-content> was induced in spleens and splenic dendritic cells (DC<\/jats:styled-content>s). DC<\/jats:styled-content> activation by lipopolysaccharide (LPS<\/jats:styled-content>), CD<\/jats:styled-content>40L or TLR<\/jats:styled-content>8 agonist significantly enhanced Arg II<\/jats:styled-content> expression without affecting Arg I expression. Conversely, DC<\/jats:styled-content> differentiating cytokines [IL<\/jats:styled-content>\u20104 and granulocyte macrophage\u2010colony\u2010stimulating factor (GM<\/jats:styled-content>\u2010CSF<\/jats:styled-content>)] yielded opposite effects. In addition, Arg I and Arg II<\/jats:styled-content> were regulated differentially during Th1 and Th17 cell polarization. Arg II<\/jats:styled-content> deficiency in mice delayed EAE<\/jats:styled-content> onset, ameliorated clinical symptoms and reduced myelin loss, accompanied by a remarkable reduction in the EAE<\/jats:styled-content>\u2010induced spinal cord expression of Th17 cell markers (IL<\/jats:styled-content>\u201017 and ROR<\/jats:styled-content>\u03b3<\/jats:italic>t). The abundance of Th17 cells and IL<\/jats:styled-content>\u201023+<\/jats:sup> cells in relevant draining lymph nodes was significantly reduced in Arg II<\/jats:styled-content> knockout mice. In activated DC<\/jats:styled-content>s, Arg II<\/jats:styled-content> deficiency significantly suppressed the expression of Th17\u2010differentiating cytokines IL<\/jats:styled-content>\u201023 and IL<\/jats:styled-content>\u20106. Interestingly, Arg II<\/jats:styled-content> deficiency did not lead to any compensatory increase in Arg I expression in vivo<\/jats:italic> and in vitro<\/jats:italic>. In conclusion, Arg II<\/jats:styled-content> was identified as a factor promoting EAE<\/jats:styled-content> likely via an Arg I\u2010independent mechanism. Arg II<\/jats:styled-content> may promote EAE<\/jats:styled-content> by enhancing DC<\/jats:styled-content> production of Th17\u2010differentiating cytokines. Specific inhibition of Arg II<\/jats:styled-content> could be a potential therapy for multiple sclerosis.<\/jats:p>","DOI":"10.1111\/imm.12926","type":"journal-article","created":{"date-parts":[[2018,3,25]],"date-time":"2018-03-25T17:53:07Z","timestamp":1522000387000},"page":"85-98","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Deficient arginase II<\/scp> expression without alteration in arginase I expression attenuated experimental autoimmune encephalomyelitis in mice"],"prefix":"10.1111","volume":"155","author":[{"given":"Mariam","family":"Choudry","sequence":"first","affiliation":[{"name":"J. L Pettis VA Medical Center Loma Linda CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaolei","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Medicine Loma Linda University School of Medicine Loma Linda CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiffany","family":"Santorian","sequence":"additional","affiliation":[{"name":"J. 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