{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:44:15Z","timestamp":1792143855221,"version":"4.4.0"},"reference-count":57,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271878"],"award-info":[{"award-number":["82271878"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971480"],"award-info":[{"award-number":["81971480"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82321002"],"award-info":[{"award-number":["82321002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2023MH015"],"award-info":[{"award-number":["ZR2023MH015"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["NCTIB2023XB02006"],"award-info":[{"award-number":["NCTIB2023XB02006"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["2024ZLGX01"],"award-info":[{"award-number":["2024ZLGX01"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cutting Edge Development Fund"},{"name":"Advanced Medical Research Institute","award":["GYY2023QY01"],"award-info":[{"award-number":["GYY2023QY01"]}],"id":[{"id":"https:\/\/ror.org\/04ppky291","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by the immune-mediated demyelination and neurodegeneration of the CNS. Phagocyte-mediated myelin debris clearance is required for remyelination. TIM-3 is highly expressed on mononuclear macrophages and promotes the phagocytosis of apoptotic cells. Here, we report that TIM-3 enhances the clearance of myelin debris in experimental autoimmune encephalomyelitis (EAE), a model of MS.<\/jats:p>\n                  <jats:p>Tim-3 knockout exacerbated EAE severity, neuroinflammation and demyelination by regulating mononuclear macrophages. TIM-3 promoted the phagocytosis and degradation of myelin debris by macrophages.<\/jats:p>\n                  <jats:p>Mechanistically, TIM-3 deficiency impaired lysosomal biogenesis and function, leading to lysosomal membrane permeabilization and disrupted lysosomal acidification, which further exacerbated neuroinflammation and demyelination. Notably, TIM-3 blocked the interaction of mTOR\u2013TFEB to inhibit TFEB phosphorylation and facilitate its nuclear translocation, followed by increased expression of lysosomal genes critical for myelin degradation. Importantly, the immunoglobulin variable (IgV) domain is necessary in TIM-3-mediated lysosomal regulation and myelin degradation.<\/jats:p>\n                  <jats:p>These findings highlight TIM-3 as a key regulator of lysosomal homeostasis and the clearance of myelin debris, suggesting that the IgV domain has promise as a therapeutic agent for treating demyelinating diseases such as MS.<\/jats:p>","DOI":"10.1093\/brain\/awag170","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T11:48:58Z","timestamp":1778240938000},"source":"Crossref","is-referenced-by-count":1,"title":["TIM-3-dependent lysosome biogenesis is required for myelin debris clearance in macrophages"],"prefix":"10.1093","author":[{"given":"Xiaodi","family":"Zhang","sequence":"first","affiliation":[{"name":"Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University , Jinan, Shandong 250012 ,","place":["P. R. China"]},{"name":"Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University , Jinan, Shandong 250012 ,","place":["P. R. China"]},{"name":"Laboratory of Infection Immunity and Disease Intervention of Shandong Province, Shandong University , Jinan, Shandong 250012 ,","place":["P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqing","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University , Jinan, Shandong 250012 ,","place":["P. R. China"]},{"name":"Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University , Jinan, Shandong 250012 ,","place":["P. R. China"]},{"name":"Laboratory of Infection Immunity and Disease Intervention of Shandong Province, Shandong University , Jinan, Shandong 250012 ,","place":["P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingxue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University , Jinan, Shandong 250012 ,","place":["P. R. China"]},{"name":"Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University , Jinan, Shandong 250012 ,","place":["P. R. China"]},{"name":"Laboratory of Infection Immunity and Disease Intervention of Shandong Province, Shandong University , Jinan, Shandong 250012 ,","place":["P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Tong","sequence":"additional","affiliation":[{"name":"Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University , Jinan, Shandong 250012 ,","place":["P. R. China"]},{"name":"Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University , Jinan, Shandong 250012 ,","place":["P. R. China"]},{"name":"Laboratory of Infection Immunity and Disease Intervention of Shandong Province, Shandong University , Jinan, Shandong 250012 ,","place":["P. R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Ren","sequence":"additional","affiliation":[{"name":"Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University , Jinan, Shandong 250012 ,","place":["P. R. China"]},{"name":"Department of Immunology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University , Jinan, Shandong 250012 ,","place":["P. R. China"]},{"name":"Laboratory of Infection Immunity and Disease Intervention of Shandong Province, Shandong University , Jinan, Shandong 250012 ,","place":["P. R. 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