{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T07:10:05Z","timestamp":1772781005013,"version":"3.50.1"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2010,5,7]],"date-time":"2010-05-07T00:00:00Z","timestamp":1273190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"National Nature Science Foundation","award":["30872298"],"award-info":[{"award-number":["30872298"]}]},{"name":"National Nature Science Foundation","award":["30972753"],"award-info":[{"award-number":["30972753"]}]},{"DOI":"10.13039\/501100012166","name":"National Basic Research Program","doi-asserted-by":"publisher","award":["2009CB521900"],"award-info":[{"award-number":["2009CB521900"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010084","name":"Independent Innovation Foundation of Shandong University","doi-asserted-by":"publisher","award":["2009TS115"],"award-info":[{"award-number":["2009TS115"]}],"id":[{"id":"10.13039\/501100010084","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,5,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Tim-4 plays an important role in preventing liver injury through inhibition of CD80, CD86, and MHC II expression and TNF-\u03b1 secretion by macrophages.<\/jats:p>\n               <jats:p>Tim-4 is expressed primarily on APCs, including macrophages, and has been shown to play a critical role in T cell regulation. However, it remains unclear whether Tim-4 also plays a role in the regulation of macrophage functions. In the present study, we investigated the effects of Tim-4 on macrophage activity in Con A-induced hepatitis in mice. We found that high levels of Tim-4 expression were associated with a diminished serum level of ALT in Con A-induced hepatitis. In addition, adoptive transfer of T4-RAW cells resulted in a significant decrease in ALT levels and Con A-induced liver injuries in mice. Concurrently, T4-RAW cells transfer displayed, markedly decreased apoptosis in liver and depressed TNF-\u03b1 secretion in serum, supporting the hypothesis that Tim-4 protects Con A-induced hepatitis by negatively regulating macrophages. Consistent with the in vivo findings, in vitro studies showed that Tim-4 overexpression in RAW264.7 cells was associated with decreased expression of CD80, CD86, and MHCII molecules and the production of TNF-\u03b1. Moreover, Tim-4 blockade promoted LPS-induced macrophage activation. In conclusion, these findings indicate that Tim-4 plays an important role in alleviating liver damage by inhibition of macrophage activity. Tim-4 pathway could be a potential target for the treatment of acute hepatitis.<\/jats:p>","DOI":"10.1189\/jlb.1209797","type":"journal-article","created":{"date-parts":[[2010,5,8]],"date-time":"2010-05-08T02:12:48Z","timestamp":1273284768000},"page":"329-336","source":"Crossref","is-referenced-by-count":26,"title":["T cell immunoglobulin- and mucin-domain-containing molecule-4 attenuates concanavalin A-induced hepatitis by regulating macrophage"],"prefix":"10.1093","volume":"88","author":[{"given":"Liyun","family":"Xu","sequence":"first","affiliation":[{"name":"Institute of Immunology, Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University School of Medicine , Shandong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianni","family":"Qi","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University School of Medicine , Shandong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peiqing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University School of Medicine , Shandong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohong","family":"Liang","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University School of Medicine , Shandong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Ju","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University School of Medicine , Shandong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University School of Medicine , Shandong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University School of Medicine , Shandong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun","family":"Guo","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University School of Medicine , Shandong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lining","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University School of Medicine , Shandong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunhong","family":"Ma","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University School of Medicine , Shandong, China"},{"name":"The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Qilu Hospital , Shandong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lifen","family":"Gao","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University School of Medicine , Shandong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2010,5,7]]},"reference":[{"key":"2023032712280588200_cit1","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1038\/ni739","article-title":"Identification of Tapr (an airway hyperreactivity regulatory locus) and the linked Tim gene family","volume":"2","author":"McIntire","year":"2001","journal-title":"Nat. Immunol."},{"key":"2023032712280588200_cit2","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/s00281-003-0141-3","article-title":"TIM-1, a novel allergy and asthma susceptibility gene","volume":"25","author":"McIntire","year":"2004","journal-title":"Springer Semin. Immunopathol."},{"key":"2023032712280588200_cit3","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1038\/nri1111","article-title":"The TIM gene family: emerging roles in immunity and disease","volume":"3","author":"Kuchroo","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"2023032712280588200_cit4","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/ni1186","article-title":"TIM-1 induces T cell activation and inhibits the development of peripheral tolerance","volume":"6","author":"Umetsu","year":"2005","journal-title":"Nat. Immunol."},{"key":"2023032712280588200_cit5","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/ni1185","article-title":"TIM-4 is the ligand for TIM-1, and the TIM-1-TIM-4 interaction regulates T cell proliferation","volume":"6","author":"Meyers","year":"2005","journal-title":"Nat. Immunol."},{"key":"2023032712280588200_cit6","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1189\/jlb.1006610","article-title":"Phenotypic differences between Th1 and Th17 cells and negative regulation of Th1 cell differentiation by IL-17","volume":"81","author":"Nakae","year":"2007","journal-title":"J. Leukoc. Biol."},{"key":"2023032712280588200_cit7","doi-asserted-by":"crossref","first-page":"2249","DOI":"10.4049\/jimmunol.178.4.2249","article-title":"Epitope-dependent effect of anti-murine TIM-1 monoclonal antibodies on T cell activity and lung immune responses","volume":"178","author":"Sizing","year":"2007","journal-title":"J. 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