{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:04:48Z","timestamp":1790697888629,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2018,6,27]],"date-time":"2018-06-27T00:00:00Z","timestamp":1530057600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004923","name":"AFM-T\u00e9l\u00e9thon","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["1R01\u2010AR\u2010071369"],"award-info":[{"award-number":["1R01\u2010AR\u2010071369"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Toll\u2010like receptor 7 (<jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>\u20107), <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>\u20108, and interferon (<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>)\u2013induced genes are expressed in patients with idiopathic inflammatory myositis. This study was undertaken to investigate whether their activation influences the natural history of the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Experimental autoimmune myositis was induced in mice by injection of the amino\u2010terminal portion of the murine histidyl\u2013transfer <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> synthetase (His<jats:styled-content style=\"fixed-case\">RS<\/jats:styled-content>). Disease was compared in the presence or the absence of the <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>\u20107\/8 agonist R\u2010848 in wild\u2010type mice and in mice that fail to express the <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u03b1\/\u03b2 receptor (<jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u03b1\/\u03b2R\u2010null mice).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Experimental autoimmune myositis induced by a single intramuscular immunization with His<jats:styled-content style=\"fixed-case\">RS<\/jats:styled-content> spontaneously abated after 7\u20138 weeks. In contrast, levels of anti\u2010His<jats:styled-content style=\"fixed-case\">RS<\/jats:styled-content> autoantibodies, endomysial\/perimysial leukocyte infiltration, and myofiber regeneration persisted at the end of the follow\u2010up period (22 weeks after immunization) in mice immunized with His<jats:styled-content style=\"fixed-case\">RS<\/jats:styled-content> in the presence of R\u2010848. Myofiber major histocompatibility complex (<jats:styled-content style=\"fixed-case\">MHC<\/jats:styled-content>) class I molecules were detectable only in mice immunized with both His<jats:styled-content style=\"fixed-case\">RS<\/jats:styled-content> and R\u2010848. <jats:styled-content style=\"fixed-case\">MHC<\/jats:styled-content> up\u2010regulation occurred early and in muscles that were not directly injected with His<jats:styled-content style=\"fixed-case\">RS<\/jats:styled-content>. Muscle <jats:styled-content style=\"fixed-case\">MHC<\/jats:styled-content> expression paralleled with leukocyte infiltration. <jats:styled-content style=\"fixed-case\">MHC<\/jats:styled-content> class I molecules were selectively up\u2010regulated in myotubes challenged with R\u2010848 in vitro. Type I <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content> was necessary for the prolonged autoantibody response and for the spreading of the autoimmune response, as demonstrated using <jats:styled-content style=\"fixed-case\">IFN<\/jats:styled-content>\u03b1\/\u03b2R\u2010null mice. Muscle infiltration was maintained in the injected muscle up to the end of the follow\u2010up period.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>\u20107\/8 activation is necessary to induce and maintain a systemic autoimmune response targeting the skeletal muscle. This experimental autoimmune myositis model reproduces many characteristics of human idiopathic inflammatory myopathies and may represent a tool for preclinical studies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40503","type":"journal-article","created":{"date-parts":[[2018,3,23]],"date-time":"2018-03-23T06:31:48Z","timestamp":1521786708000},"page":"1276-1287","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Exacerbation of Murine Experimental Autoimmune Myositis by Toll\u2010Like Receptor 7\/8"],"prefix":"10.1002","volume":"70","author":[{"given":"Clara","family":"Sciorati","sequence":"first","affiliation":[{"name":"IRCCS Ospedale San Raffaele Scientific Institute Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Monno","sequence":"additional","affiliation":[{"name":"IRCCS Ospedale San Raffaele Scientific Institute Milan 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