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It was reported that IL-36 plays a role in immune diseases. However, it remains unclear how IL-36 regulates inflammation. To determine the role of IL-36\/IL-36R signaling pathways, we established an acute hepatitis mouse model (C57BL\/6) by i.v. injection of the plant lectin Con A. We found that the levels of IL-36 were increased in the liver after Con A injection. Our results demonstrated the infiltrated neutrophils, but not the hepatocytes, were the main source of IL-36 in the liver. Using the IL-36R\u2212\/\u2212 mouse model (H-2b), we surprisingly found that the absence of IL-36 signals led to aggravated liver injury, as evidenced by increased mortality, elevated serum alanine aminotransferase and aspartate aminotransferase levels, and severe liver pathological changes. Further investigations demonstrated that a lack of IL-36 signaling induced intrahepatic activation of CD4+ and CD8+ T lymphocytes and increased the production of inflammatory cytokines. In addition, IL-36R\u2212\/\u2212 mice had reduced T regulatory cell numbers and chemokines in the liver. Together, our results from the mouse model suggested a vital role of IL-36 in regulating T cell function and homeostasis during liver inflammation.<\/jats:p>","DOI":"10.4049\/jimmunol.2100481","type":"journal-article","created":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T15:30:29Z","timestamp":1642606229000},"page":"861-869","source":"Crossref","is-referenced-by-count":13,"title":["The Protective Role of IL-36\/IL-36R Signal in Con A\u2013Induced Acute Hepatitis"],"prefix":"10.1093","volume":"208","author":[{"given":"Xiaofang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University , Changsha, Hunan,","place":["China"]},{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9557-1847","authenticated-orcid":false,"given":"Yuejin","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, TX"},{"name":"Institute for Human Infections and Immunity, University of Texas Medical Branch , Galveston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Medical Branch , Galveston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9573-9849","authenticated-orcid":false,"given":"Biao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, TX"},{"name":"Department of Histology and Embryology, Guangdong Medical University , Zhanjiang, Guangdong,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3370-3434","authenticated-orcid":false,"given":"Lynn","family":"Soong","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, TX"},{"name":"Institute for Human Infections and Immunity, University of Texas Medical Branch , Galveston, TX"},{"name":"Department of Pathology, University of Texas Medical Branch , Galveston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiyang","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Texas Medical Branch , Galveston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Panpan","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University , Changsha, Hunan,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuegong","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University , Changsha, Hunan,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5084-4437","authenticated-orcid":false,"given":"Jiaren","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Texas Medical Branch , Galveston, TX"},{"name":"Institute for Human Infections and Immunity, University of Texas Medical Branch , Galveston, TX"},{"name":"Department of Pathology, University of Texas Medical Branch , Galveston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,2,15]]},"reference":[{"key":"2025021008542843100_r1","doi-asserted-by":"crossref","first-page":"13677","DOI":"10.1074\/jbc.M400117200","article-title":"Interleukin (IL)-1F6, IL-1F8, and IL-1F9 signal through IL-1Rrp2 and IL-1RAcP to activate the pathway leading to NF-kappaB and MAPKs","volume":"279","author":"Towne","year":"2004","journal-title":"J. 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