{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T14:31:38Z","timestamp":1790346698425,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T00:00:00Z","timestamp":1721174400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K09069"],"award-info":[{"award-number":["21K09069"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19KK0224"],"award-info":[{"award-number":["19KK0224"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K08971"],"award-info":[{"award-number":["22K08971"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K09160"],"award-info":[{"award-number":["22K09160"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19KK0196"],"award-info":[{"award-number":["19KK0196"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","award":["2021042945"],"award-info":[{"award-number":["2021042945"]}],"id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2024,10]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Intensive care unit\u2010acquired weakness (ICU\u2010AW) is a syndrome characterized by a long\u2010term muscle weakness often observed in sepsis\u2010surviving patients during the chronic phase. Although ICU\u2010AW is independently associated with increased mortality, effective therapies have yet to be established. Programmed death\u20101 (PD\u20101) inhibitors have attracted attention as potential treatments for reversing immune exhaustion in sepsis; however, its impact on ICU\u2010AW remains to be elucidated. Here, we study how PD\u20101 deficiency affects sepsis\u2010induced skeletal muscle dysfunction in a preclinical sepsis model.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Chronic sepsis model was developed by treating wild\u2010type (WT) and PD\u20101 knockout (KO) mice with caecal slurry, followed by resuscitation with antibiotics and saline. Mice were euthanized on days 15\u201317. Body weights, muscle weights, and limb muscle strengths were measured. Interleukin 13 (IL\u201013)\u00a0and PD\u20101 expressions were examined by flow cytometry. Messenger RNA (mRNA) expressions of slow\u2010twitch muscles were measured by reverse transcription and quantitative polymerase chain reaction (RT\u2010qPCR). In an\n in vitro<\/jats:italic>\n study, C2C12 myotubes were treated with lipopolysaccharide (LPS) and recombinant IL\u201013 followed by gene expression measurements.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n WT septic mice exhibited decreased muscle weight (quadriceps,\n P<\/jats:italic>\n \u00a0<\u00a00.01; gastrocnemius,\n P<\/jats:italic>\n \u00a0<\u00a00.05; and tibialis anterior,\n P<\/jats:italic>\n \u00a0<\u00a00.01) and long\u2010term muscle weakness (\n P<\/jats:italic>\n \u00a0<\u00a00.0001), whereas PD\u20101 KO septic mice did not exhibit any reduction in muscle weights and strengths. Slow\u2010twitch specific mRNAs, including myoglobin (\n Mb<\/jats:italic>\n ), troponin I type 1 (\n Tnni1<\/jats:italic>\n ), and myosin heavy chain 7 (\n Myh7<\/jats:italic>\n ) were decreased in WT skeletal muscle (\n Mb<\/jats:italic>\n ,\n P<\/jats:italic>\n \u00a0<\u00a00.0001;\n Tnni1<\/jats:italic>\n ,\n P<\/jats:italic>\n \u00a0<\u00a00.05; and\n Myh7<\/jats:italic>\n ,\n P<\/jats:italic>\n \u00a0<\u00a00.05) after sepsis induction, but mRNA expressions of Tnni1 and Myh7 were increased in PD\u20101 KO septic mice (\n Mb<\/jats:italic>\n , not significant;\n Tnni1<\/jats:italic>\n ,\n P<\/jats:italic>\n \u00a0<\u00a00.0001; and\n Myh7<\/jats:italic>\n ,\n P<\/jats:italic>\n \u00a0<\u00a00.05). Treatment of C2C12 myotube cells with LPS decreased the expression of slow\u2010twitch mRNAs, which was restored by IL\u201013 (\n Mb<\/jats:italic>\n ,\n P<\/jats:italic>\n \u00a0<\u00a00.0001;\n Tnni1<\/jats:italic>\n ,\n P<\/jats:italic>\n \u00a0<\u00a00.001; and\n Myh7<\/jats:italic>\n ,\n P<\/jats:italic>\n \u00a0<\u00a00.05). IL\u201013 production was significantly higher in ILC2s compared to T cells in skeletal muscle (\n P<\/jats:italic>\n \u00a0<\u00a00.05). IL\u201013\u2010producing ILC2s in skeletal muscle were examined and found to increase in PD\u20101 KO septic mice, compared with WT septic mice (\n P<\/jats:italic>\n \u00a0<\u00a00.05). ILC2\u2010derived IL\u201013 was increased by PD\u20101 KO septic mice and thought to protect the muscles from experimental ICU\u2010AW.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Long\u2010term muscle weakness in experimental ICU\u2010AW was ameliorated in PD\u20101 KO mice. ILC2\u2010derived IL\u201013 production in skeletal muscles was increased in PD\u20101 KO mice, thereby suggesting that IL\u201013 alleviates muscle weakness during sepsis. This study demonstrates the effects of PD\u20101 blockade in preserving muscle strength during sepsis through an increase in ILC2\u2010derived IL\u201013 and may be an attractive therapeutic target for sepsis\u2010induced ICU\u2010AW.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.13548","type":"journal-article","created":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T06:49:18Z","timestamp":1721198958000},"page":"1999-2012","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Roles of programmed death\u20101 and muscle innate lymphoid cell\u2010derived interleukin 13 in sepsis\u2010induced intensive care unit\u2010acquired weakness"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7040-1307","authenticated-orcid":false,"given":"Yuichi","family":"Akama","sequence":"first","affiliation":[{"name":"Department of Molecular Pathobiology and Cell Adhesion Biology Mie University Graduate School of Medicine Tsu Japan"},{"name":"Department of Emergency and Critical Care Medicine Mie University Graduate School of Medicine Tsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4288-5893","authenticated-orcid":false,"given":"Eun Jeong","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathobiology and Cell Adhesion Biology Mie University Graduate School of Medicine Tsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Satoh\u2010Takayama","sequence":"additional","affiliation":[{"name":"Precision Immune Regulation RIKEN Research Unit, Center for Integrative Medical Sciences RIKEN Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathobiology and Cell Adhesion Biology Mie University Graduate School of Medicine Tsu Japan"},{"name":"Department of Thoracic and Cardiovascular Surgery Mie University Graduate School of Medicine Tsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3920-9939","authenticated-orcid":false,"given":"Eiji","family":"Kawamoto","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathobiology and Cell Adhesion Biology Mie University Graduate School of Medicine Tsu Japan"},{"name":"Department of Emergency and Critical Care Medicine Mie University Graduate School of Medicine Tsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arong","family":"Gaowa","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathobiology and Cell Adhesion Biology Mie University Graduate School of Medicine Tsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eri","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathobiology and Cell Adhesion Biology Mie University Graduate School of Medicine Tsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7696-8128","authenticated-orcid":false,"given":"Satoshi","family":"Oikawa","sequence":"additional","affiliation":[{"name":"Faculty of Sport Sciences Waseda University Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Disaster and Emergency and Critical Care Medicine Kobe University Graduate School of Medicine Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeaki","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Emergency and Critical Care Medicine Wakayama Medical University Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Akimoto","sequence":"additional","affiliation":[{"name":"Faculty of Sport Sciences Waseda University Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Emergency and Critical Care Medicine Mie University Graduate School of Medicine Tsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motomu","family":"Shimaoka","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathobiology and Cell Adhesion Biology Mie University Graduate School of Medicine Tsu 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of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.13548","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T22:47:46Z","timestamp":1727909266000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.13548"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,17]]},"references-count":40,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,10]]}},"alternative-id":["10.1002\/jcsm.13548"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.13548","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,17]]},"assertion":[{"value":"2023-09-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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