{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T20:35:00Z","timestamp":1761597300160},"reference-count":61,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2011,9,13]],"date-time":"2011-09-13T00:00:00Z","timestamp":1315872000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Immunol Cell Biol"],"published-print":{"date-parts":[[2012,7]]},"abstract":"<jats:p>Invariant natural killer T (<jats:italic>i<\/jats:italic>NKT) cells are innate lymphocytes with unique reactivity to glycolipid antigens bound to non\u2010polymorphic CD1d molecules. They are capable of rapidly releasing pro\u2010 and\/or anti\u2010inflammatory cytokines and constitute attractive targets for immunotherapy of a wide range of diseases including autoimmune disorders. In this study, we have explored the beneficial effects of OCH, a Th2\u2010polarizing glycolipid agonist of <jats:italic>i<\/jats:italic>NKT cells, in a humanized mouse model of rheumatoid arthritis (RA) in which citrullinated human proteins are targeted by autoaggressive immune responses in mice expressing an RA susceptibility human leukocyte antigen (HLA) DR4 molecule. We found for the first time that treatment with OCH both prevents and cures citrulline\u2010induced autoimmune arthritis as evidenced by resolved ankle swelling and reversed histopathological changes associated with arthritis. Also importantly, OCH treatment blocked the arthritogenic capacity of citrullinated antigen\u2010experienced splenocytes without compromising their global responsiveness or altering the proportion of splenic naturally occurring CD4<jats:sup>+<\/jats:sup>CD25<jats:sup>+<\/jats:sup>FoxP3<jats:sup>+<\/jats:sup> regulatory T cells. Interestingly, administering the Th1\u2010promoting <jats:italic>i<\/jats:italic>NKT cell glycolipid ligand <jats:italic>\u03b1<\/jats:italic>\u2010C\u2010galactosylceramide into HLA\u2010DR4 transgenic mice increased the incidence of arthritis in these animals and exacerbated their clinical symptoms, strongly suggesting a role for Th1 responses in the pathogenesis of citrulline\u2010induced arthritis. Therefore, our findings indicate a role for Th1\u2010mediated immunopathology in citrulline\u2010induced arthritis and provide the first evidence that <jats:italic>i<\/jats:italic>NKT cell manipulation by Th2\u2010skewing glycolipids may be of therapeutic value in this clinically relevant model, a finding that is potentially translatable to human RA.<\/jats:p>","DOI":"10.1038\/icb.2011.78","type":"journal-article","created":{"date-parts":[[2011,9,13]],"date-time":"2011-09-13T09:57:16Z","timestamp":1315907836000},"page":"630-639","source":"Crossref","is-referenced-by-count":9,"title":["Preventing and curing citrulline\u2010induced autoimmune arthritis in a humanized mouse model using a Th2\u2010polarizing <i>i<\/i>NKT cell agonist"],"prefix":"10.1111","volume":"90","author":[{"given":"Kyle M","family":"Walker","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Western Ontario  London Ontario 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