{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T13:36:33Z","timestamp":1790429793828,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T00:00:00Z","timestamp":1617235200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:p>T\u2010cell immunoglobulin\u2010 and mucin\u2010domain\u2010containing molecule\u20103 (Tim\u20103) mediates T\u2010cell suppression in various autoimmune diseases, such as chronic inflammatory liver disease. However, the regulatory effect of Tim\u20103 on Th17 cells in autoimmune hepatitis (AIH) is incompletely understood. Here, we studied the expression and function of Tim\u20103 in T cells in AIH patients and in a Con A (concanavalin A)\u2010induced mouse AIH model. We report that the frequency of CD4<jats:sup>+<\/jats:sup>Tim\u20103<jats:sup>+<\/jats:sup> T cells in peripheral blood samples of AIH patients was lower than that in the control group. The p38\/MKP\u20101 and p\u2010JNK pathways were activated, and the expression of interleukin\u201017A protein was elevated in patients with AIH. Furthermore, the extent of pathological damage in the livers of mice with a blocked Tim\u20103 signaling pathway (anti\u2010Tim\u20103 group) was markedly increased and correlated with elevated alanine aminotransferase and aspartate aminotransferase levels. In addition, the frequency of CD4<jats:sup>+<\/jats:sup> IL\u201017<jats:sup>+<\/jats:sup> T (Th17) cells in the anti\u2010Tim\u20103 group was increased, while that in mice with blocked p38 activity was decreased. Finally, the expression of MKP\u20101 (p\u2010p38) gradually increased in the control, Con A, and anti\u2010Tim\u20103 groups, but the levels of interleukin\u201017A were decreased in the p38\u2010blocked group. In summary, our results suggest that Tim\u20103 suppresses AIH by regulating Th17 cells through the p38\/MKP\u20101 pathway.<\/jats:p>","DOI":"10.1002\/2211-5463.13148","type":"journal-article","created":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T06:39:21Z","timestamp":1615963161000},"page":"1406-1416","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Tim\u20103 suppresses autoimmune hepatitis via the p38\/MKP\u20101 pathway in Th17 cells"],"prefix":"10.1002","volume":"11","author":[{"given":"Hongwei","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases Affiliated Taizhou Hospital of Wenzhou Medical University Linhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyue","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Affiliated Taizhou Hospital of Wenzhou Medical University Linhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengya","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pathology Affiliated Taizhou Hospital of Wenzhou Medical University Linhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiji","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Affiliated Taizhou Hospital of Wenzhou Medical University Linhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenjun","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Affiliated Taizhou Hospital of Wenzhou Medical University Linhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4961-7437","authenticated-orcid":false,"given":"Jiansheng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Affiliated Taizhou Hospital of Wenzhou Medical University Linhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2018.10.007"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.06.030"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00163"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.2174\/1573396310666141114230147"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-016-9767-9"},{"key":"e_1_2_10_7_1","first-page":"1022","article-title":"Epidemiology and causes of death in a Swedish cohort of patients with autoimmune hepatitis","volume":"52","author":"Danielsson Borssen A","year":"2017","journal-title":"Scand J Gastroenterol"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.11.026"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2012.11.002"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26583"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni988"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12520"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/415536a"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-018-0032-0"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2008.10.007"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25682"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2020.05.014"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1006\/cyto.2002.1948"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2002-35704"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2018.04.036"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13071-019-3788-x"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.03.005"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2015.11.004"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115836"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v18.i2.119"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2011.05.003"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2871"},{"key":"e_1_2_10_28_1","article-title":"Autoimmune hepatitis: progress from global immunosuppression to personalised regulatory T cell therapy","volume":"2016","author":"Than NN","year":"2016","journal-title":"Can J Gastroenterol Hepatol"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2004.03.008"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27884"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2018.17"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018909"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjms.2017.01.019"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.2147\/DMSO.S236127"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1089\/jwh.2015.5214"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.4143\/crt.2018.105"}],"container-title":["FEBS Open Bio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/2211-5463.13148","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/2211-5463.13148","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/2211-5463.13148","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T09:38:36Z","timestamp":1704965916000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1002\/2211-5463.13148"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4]]},"references-count":35,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,5]]}},"alternative-id":["10.1002\/2211-5463.13148"],"URL":"https:\/\/doi.org\/10.1002\/2211-5463.13148","archive":["Portico"],"relation":{},"ISSN":["2211-5463","2211-5463"],"issn-type":[{"value":"2211-5463","type":"print"},{"value":"2211-5463","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4]]},"assertion":[{"value":"2021-03-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}