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In this study, we found that T cell Ig and mucin domain protein 3 (Tim\u20103) and TLR4 receptors play important roles in CCl4\u2010induced acute liver injury. Tim\u20103 is a negative regulator that is expressed by T cells and macrophages. Using antibodies against Tim\u20103 (anti\u2010Tim\u20103 Ab), we studied the Tim\u20103 signal in an animal model of acute liver injury and found that a large number of inflammatory factors were upregulated. In vitro experimental data shown that anti\u2010Tim\u20103 Ab treatment increased interferon\u2010\u0263 production by concanavalin A (ConA)\u2010stimulated spleen T cells, and we found that the expression level of interleukin (IL)\u20106 was increased in a macrophage\/spleen T cell coculture system, while administration of galectin\u20109 (Gal\u20109, a Tim\u20103 ligand) reduced the IL\u20106 production. This indicates the importance of the Tim\u20103\/Gal\u20109 signalling pathway in maintaining hepatic homeostasis. The Tim\u20103 signalling pathway inhibits TLR4\u2010mediated NF\u2010\u03baB activity, and an anti\u2010Tim\u20103 Ab does not affect the liver injury in TLR4\u2010deficient mice. Regulation between Tim\u20103 and TLR4 determines the severity of liver damage. The negative regulation of Tim\u20103 reflects the protective mechanisms of patients with impaired liver function, and these results provide important information about innate and adaptive responses in the regulation of liver damage. This finding is potentially important for the study of early liver injury.<\/jats:p>","DOI":"10.1111\/sji.12851","type":"journal-article","created":{"date-parts":[[2019,11,16]],"date-time":"2019-11-16T14:14:44Z","timestamp":1573913684000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Cross\u2010regulation by TLR4 and T cell Ig mucin\u20103 determines severity of liver injury in a CCl4\u2010induced mouse model"],"prefix":"10.1111","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5875-6463","authenticated-orcid":false,"given":"Lizhen","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Immunology College of Basic Medicine Qingdao University Qingdao Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Immunology College of Basic Medicine Qingdao University Qingdao 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