{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T10:19:44Z","timestamp":1792405184633,"version":"4.4.0"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2016,6,29]],"date-time":"2016-06-29T00:00:00Z","timestamp":1467158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2016,6,29]],"date-time":"2016-06-29T00:00:00Z","timestamp":1467158400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:p>During liver injury, hepatocytes secrete exosomes that include diverse types of self\u2010RNAs. Recently, self\u2010noncoding RNA has been recognized as an activator of Toll\u2010like receptor 3 (TLR3). However, the roles of hepatic exosomes and TLR3 in liver fibrosis are not yet fully understood. Following acute liver injury and early\u2010stage liver fibrosis induced by a single or 2\u2010week injection of carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>), increased interleukin (IL)\u201017A production was detected primarily in hepatic \u03b3\u03b4 T cells in wild\u2010type (WT) mice. However, liver fibrosis and IL\u201017A production by \u03b3\u03b4 T cells were both significantly attenuated in TLR3 knockout (KO) mice compared with WT mice. More interestingly, IL\u201017A\u2010producing \u03b3\u03b4 T cells were in close contact with activated hepatic stellate cells (HSCs), suggesting a role for HSCs in IL\u201017A production by \u03b3\u03b4 T cells.<jats:italic toggle=\"yes\">In vitro<\/jats:italic>treatments with exosomes derived from CCl<jats:sub>4<\/jats:sub>\u2010treated hepatocytes significantly increased the expression of IL\u201017A, IL\u20101\u03b2, and IL\u201023 in WT HSCs but not in TLR3 KO HSCs. Furthermore, IL\u201017A production by \u03b3\u03b4 T cells was substantially increased upon coculturing with exosome\u2010treated WT HSCs or conditioned medium from TLR3\u2010activated WT HSCs. However, similar increases were not detected when \u03b3\u03b4 T cells were cocultured with exosome\u2010treated HSCs from IL\u201017A KO or TLR3 KO mice. Using reciprocal bone marrow transplantation between WT and TLR3 KO mice, we found that TLR3 deficiency in HSCs contributed to decreased IL\u201017A production by \u03b3\u03b4 T cells, as well as liver fibrosis.<jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: In liver injury, the exosome\u2010mediated activation of TLR3 in HSCs exacerbates liver fibrosis by enhancing IL\u201017A production by \u03b3\u03b4 T cells, which might be associated with HSC stimulation by unknown self\u2010TLR3 ligands from damaged hepatocytes. Therefore, TLR3 might be a novel therapeutic target for liver fibrosis. (H<jats:sc>epatology<\/jats:sc>2016;64:616\u2010631)<\/jats:p>","DOI":"10.1002\/hep.28644","type":"journal-article","created":{"date-parts":[[2016,5,14]],"date-time":"2016-05-14T08:23:17Z","timestamp":1463214197000},"page":"616-631","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":172,"title":["Exosome\u2010mediated activation of toll\u2010like receptor 3 in stellate cells stimulates interleukin\u201017 production by \u03b3\u03b4 T cells in liver fibrosis"],"prefix":"10.1097","volume":"64","author":[{"given":"Wonhyo","family":"Seo","sequence":"first","affiliation":[{"name":"Laboratory of Liver Research,Biomedical Science and Engineering Interdisciplinary Program,KAIST,Daejeon,Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyuk Soo","family":"Eun","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Research,Graduate School of Medical Science and Engineering,KAIST,Daejeon,Republic of Korea"},{"name":"Department of Internal Medicine,Chungnam National University School of Medicine,Daejeon,Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So Yeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Research,Biomedical Science and Engineering Interdisciplinary Program,KAIST,Daejeon,Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyon\u2010Seung","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine,Chungnam National University School of Medicine,Daejeon,Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young\u2010Sun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine,Korea University College of Medicine,Seoul,Republic of 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Chang","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences,Korea Advanced Institute of Science and Technology,Daejeon,Republic of Korea"},{"name":"Intelligent Synthetic Biology Center,Daejeon,Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong\u2010Mahn","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences,Korea Advanced Institute of Science and Technology,Daejeon,Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keun\u2010Gyu","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine,School of Medicine,Kyungpook National University,Daegu,Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won\u2010Il","family":"Jeong","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Research,Biomedical Science and Engineering Interdisciplinary 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