{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T23:54:05Z","timestamp":1785196445549,"version":"3.55.0"},"reference-count":52,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T00:00:00Z","timestamp":1729468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012002","name":"Descente and Ishimoto Memorial Foundation for the Promotion of Sports Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008731","name":"Nakatomi Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Idiopathic inflammatory myopathies (IIMs) are systemic autoimmune diseases characterised by muscle weakness. Although multiple physiological and pathological processes are associated with IIMs, T\u2010lymphocyte infiltration into muscle plays a key role in the development and exacerbation of IIMs. Nuclear factor erythroid 2\u2010related factor 2 (Nrf2) is a key transcription factor that regulates inflammatory responses; therefore, muscle Nrf2 may serve an important role in the development of IIMs. In this study, we demonstrated that experimental autoimmune myositis (EAM) causes loss of muscle mass and function in oxidative and glycolytic muscles in C57BL\/6 mice. EAM increased CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T\u2010lymphocyte infiltration, as well as interferon\u2010gamma (IFN\u2010\u03b3) and tumour necrosis factor\u2010alpha (TNF\u2010\u03b1) mRNA expression in oxidative soleus and glycolytic extensor digitorum longus muscles, along with elevated chemokine mRNA levels (i.e. CCL3, CCL5, CXCL9, CXCL10 and CXCL16). IFN\u2010\u03b3 and TNF\u2010\u03b1 treatments increased the mRNA expression levels of these chemokines in C2C12 myotubes. EAM also increased phosphorylated Nrf2 at Ser40 in soleus and glycolytic white vastus lateralis muscle. Although the expression of several chemokines was affected by Nrf2 activation following tert\u2010butylhydroquinone treatment or Keap1 knockdown, CCL5 mRNA expression significantly increased in C2C12 myotubes and mouse skeletal muscle. Moreover, muscle\u2010specific Nrf2 knockout in mice attenuates EAM\u2010induced loss of muscle mass and function, which was associated with the inhibition of CCL5 mRNA expression, CD8<jats:sup>+<\/jats:sup> T\u2010lymphocyte infiltration and IFN\u2010\u03b3 mRNA expression. Collectively, these findings reveal that regulating Nrf2 activity is a promising therapeutic approach for treating IIM\u2010mediated muscle weakness.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16376-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Experimental autoimmune myositis (EAM) causes loss of muscle mass and function.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Loss of muscle mass and function in EAM were associated with increased chemokine mRNA expression (i.e. CCL3, CCL5, CXCL9, CXCL10 and CXCL16), T\u2010lymphocyte infiltration and inflammatory cytokine mRNA expression (i.e. IFN\u2010\u03b3 and TNF\u2010\u03b1) in the skeletal muscle.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>EAM activated Nrf2 in muscle and increased Nrf2 activity <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> increased CCL5 mRNA expression.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Muscle\u2010specific Nrf2 knockout in mice attenuated EAM\u2010induced muscle weakness by inhibiting CCL5 mRNA expression, CD8<jats:sup>+<\/jats:sup> T\u2010lymphocyte migration and IFN\u2010\u03b3 mRNA expression in muscles.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results provide further evidence for the potential therapeutic targeting of Nrf2 to mitigate EAM\u2010induced muscle weakness.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp286534","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T08:49:55Z","timestamp":1729500595000},"page":"6189-6207","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Nrf2 deficiency in muscle attenuates experimental autoimmune myositis\u2010induced muscle weakness"],"prefix":"10.1113","volume":"602","author":[{"given":"Koichi","family":"Himori","sequence":"first","affiliation":[{"name":"Graduate School of Science Nagoya City University  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mami","family":"Yamada","sequence":"additional","affiliation":[{"name":"Graduate School of Science Nagoya City University  Nagoya 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