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We hypothesized that the injured muscle fibers release pro-inflammatory molecules, which would further accelerate CD8\n                    <jats:sup>+<\/jats:sup>\n                    cytotoxic T lymphocytes-induced muscle injury, and inhibition of the cell death of muscle fibers could be a novel therapeutic strategy to suppress both muscle injury and inflammation in polymyositis. Here, we show that the pattern of cell death of muscle fibers in polymyositis is FAS ligand-dependent necroptosis, while that of satellite cells and myoblasts is perforin 1\/granzyme B-dependent apoptosis, using human muscle biopsy specimens of polymyositis patients and models of polymyositis in vitro and in vivo. Inhibition of necroptosis suppresses not only CD8\n                    <jats:sup>+<\/jats:sup>\n                    cytotoxic T lymphocytes-induced cell death of myotubes but also the release of inflammatory molecules including HMGB1. Treatment with a necroptosis inhibitor or anti-HMGB1 antibodies ameliorates myositis-induced muscle weakness as well as muscle cell death and inflammation in the muscles. Thus, targeting necroptosis in muscle cells is a promising strategy for treating polymyositis providing an alternative to current therapies directed at leukocytes.\n                  <\/jats:p>","DOI":"10.1038\/s41467-021-27875-4","type":"journal-article","created":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T06:02:59Z","timestamp":1641794579000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Targeting necroptosis in muscle fibers ameliorates inflammatory myopathies"],"prefix":"10.1038","volume":"13","author":[{"given":"Mari","family":"Kamiya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumitaka","family":"Mizoguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimito","family":"Kawahata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dengli","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Nishibori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8528-4361","authenticated-orcid":false,"given":"Jessica","family":"Day","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8382-6358","authenticated-orcid":false,"given":"Cynthia","family":"Louis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7050-6822","authenticated-orcid":false,"given":"Ian P.","family":"Wicks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Kohsaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6171-2077","authenticated-orcid":false,"given":"Shinsuke","family":"Yasuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,10]]},"reference":[{"key":"27875_CR1","doi-asserted-by":"publisher","first-page":"398","DOI":"10.3109\/14397595.2015.1091137","volume":"26","author":"H Tomimitsu","year":"2016","unstructured":"Tomimitsu, H. et al. 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