{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T14:32:07Z","timestamp":1780065127805,"version":"3.54.0"},"reference-count":13,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Introduction\/Aims<\/jats:title><jats:p>Selective depletion of muscle\u2010infiltrating pathogenic T cells is a promising therapeutic approach for inclusion body myositis (IBM), but no ideal cell surface antigen that is selectively expressed on these cells has been identified. LAG3 is expressed on highly differentiated, recently activated T cells, but detailed expression profiles in IBM patients have not been reported. This study was intended to bridge this research gap.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>First, biobank\u2010stored skeletal muscle tissue samples (biceps or quadriceps) of six IBM patients, which had been biopsied for diagnosis, were used for immunohistochemistry (IHC) for T\u2010cell antigens including LAG3 and CD244, a surface marker of late\u2010differentiated lymphocytes. Next, eight IBM patients were enrolled, and fluorescence\u2010activated cell sorting (FACS) was performed on their blood to count the LAG3\u2010expressing cells. Muscle magnetic resonance imaging (MRI) and whole\u2010blood microarrays were also performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Upon analyzing LAG3 expression on 41\u2013128 CD3<jats:sup>+<\/jats:sup> lymphocytes and 11\u201386 CD244<jats:sup>+<\/jats:sup> lymphocytes counted in the regions of interest (ROIs) for each biobank\u2010stored sample, their positivity rates were 19.3%\u201348.0% and 41.7%\u201375.6%, respectively. In contrast, notably few LAG3\u2010expressing cells were present in the blood. Both CD8<jats:sup>+<\/jats:sup>LAG3<jats:sup>+<\/jats:sup> and CD8<jats:sup>\u2212<\/jats:sup>LAG3<jats:sup>+<\/jats:sup> cells constituted less than 0.1% of total T cells, although muscle MRI and blood microarray, showing upregulation of the proinflammatory genes GBP1 and GBP5, revealed both myositis and systemic inflammatory conditions in these patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Agents that deplete LAG3<jats:sup>+<\/jats:sup> lymphocytes, such as anti\u2010LAG3 antibody that induces antibody\u2010dependent cell cytotoxicity, are potential drug candidates with a favorable efficacy\/safety balance for treating IBM.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.28452","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T05:14:18Z","timestamp":1749446058000},"page":"443-449","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>LAG3<\/scp> Is Expressed on Muscle\u2010Infiltrating Cytotoxic T Cells, but Scarce on Circulating T Cells, in Patients With Inclusion Body Myositis"],"prefix":"10.1002","volume":"72","author":[{"given":"Ryuta","family":"Mukasa","sequence":"first","affiliation":[{"name":"Translational Science Department II Daiichi Sankyo Company, Limited  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiya","family":"Ogata","sequence":"additional","affiliation":[{"name":"R&amp;D Resource Management Department Daiichi Sankyo Company, Limited  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2568-9505","authenticated-orcid":false,"given":"Naoki","family":"Kiyosawa","sequence":"additional","affiliation":[{"name":"Translational Science Department II Daiichi Sankyo Company, Limited  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Shibutani","sequence":"additional","affiliation":[{"name":"Translational Research Laboratories, Daiichi Sankyo Company, Limited  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinori","family":"Kashimoto","sequence":"additional","affiliation":[{"name":"Translational Research Laboratories, Daiichi Sankyo Company, Limited  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Translational Science Department I Daiichi Sankyo Company, Limited  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Midori","family":"Kusama","sequence":"additional","affiliation":[{"name":"Department of Radiology National Center of Neurology and Psychiatry  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hotake","family":"Takizawa","sequence":"additional","affiliation":[{"name":"Department of Neurology National Center of Neurology and Psychiatry  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Radiology National Center of Neurology and Psychiatry  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9452-112X","authenticated-orcid":false,"given":"Ichizo","family":"Nishino","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Research National Institute of Neuroscience, National Center of Neurology and Psychiatry  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madoka","family":"Mori\u2010Yoshimura","sequence":"additional","affiliation":[{"name":"Department of Neurology National Center of Neurology 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&amp; Nerve"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.28452","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T14:14:29Z","timestamp":1754921669000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mus.28452"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,9]]},"references-count":13,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1002\/mus.28452"],"URL":"https:\/\/doi.org\/10.1002\/mus.28452","archive":["Portico"],"relation":{},"ISSN":["0148-639X","1097-4598"],"issn-type":[{"value":"0148-639X","type":"print"},{"value":"1097-4598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,9]]},"assertion":[{"value":"2024-04-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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