{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T16:01:45Z","timestamp":1772726505901,"version":"3.50.1"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T00:00:00Z","timestamp":1512086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Promising results of immune checkpoint inhibitors have indicated the use of immunotherapy against malignant tumors. However, they cause serious side effects, including autoimmune diseases and pneumonitis. T cell Ig and mucin domain (TIM)-3 is a new candidate immune checkpoint molecule; however, the potential toxicity associated with anti\u2013TIM-3 treatment is unknown. In this study, we investigated the pathological contribution of anti\u2013TIM-3 mAb in a bleomycin-induced lung inflammation and fibrosis model. Anti\u2013TIM-3\u2013treated mice showed more severe inflammation and peribronchiolar fibrosis compared with control IgG-treated mice. Anti\u2013TIM-3 mAb was associated with increased numbers of myofibroblasts, collagen deposition, and TGF-\u03b21 production in lungs. TIM-3 expression was only detected on alveolar macrophages that protect against fibrosis by apoptotic cell clearance. Treatment with anti\u2013TIM-3 mAb inhibited the phagocytic ability of alveolar macrophages in vivo, resulting in the defective clearance of apoptotic cells in lungs. In summary, anti\u2013TIM-3 mAb treatment might cause pneumonitis and it should be used with caution in clinical settings.<\/jats:p>","DOI":"10.4049\/jimmunol.1700059","type":"journal-article","created":{"date-parts":[[2017,10,23]],"date-time":"2017-10-23T20:40:36Z","timestamp":1508791236000},"page":"3733-3737","source":"Crossref","is-referenced-by-count":30,"title":["Cutting Edge: Anti\u2013TIM-3 Treatment Exacerbates Pulmonary Inflammation and Fibrosis in Mice"],"prefix":"10.1093","volume":"199","author":[{"given":"Takuma","family":"Isshiki","sequence":"first","affiliation":[{"name":"Department of Immunology, Juntendo University School of Medicine , Tokyo 113-8421,","place":["Japan"]},{"name":"Department of Respiratory Medicine, Toho University Omori Medical Centre , Tokyo 143-8541,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisaya","family":"Akiba","sequence":"additional","affiliation":[{"name":"Department of Immunology, Juntendo University School of Medicine , Tokyo 113-8421,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masafumi","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Frontier Research Institute for Interdisciplinary Sciences, Tohoku University , Sendai 980-8578,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0962-5731","authenticated-orcid":false,"given":"Norihiro","family":"Harada","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Juntendo University School of Medicine , Tokyo 113-8421,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ko","family":"Okumura","sequence":"additional","affiliation":[{"name":"Department of Immunology, Juntendo University School of Medicine , Tokyo 113-8421,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sakae","family":"Homma","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Toho University Omori Medical Centre , Tokyo 143-8541,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sachiko","family":"Miyake","sequence":"additional","affiliation":[{"name":"Department of Immunology, Juntendo University School of Medicine , Tokyo 113-8421,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2017,12,1]]},"reference":[{"key":"2025030614532055400_r1","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.cell.2015.03.030","article-title":"Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential","volume":"161","author":"Sharma","year":"2015","journal-title":"Cell"},{"key":"2025030614532055400_r2","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/nrd4591","article-title":"Combination cancer immunotherapy and new immunomodulatory targets","volume":"14","author":"Mahoney","year":"2015","journal-title":"Nat. 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