DC Field | Value | Language |
---|---|---|
dc.contributor.author | Seo, Wonhyo | ko |
dc.contributor.author | Eun, Hyuk Soo | ko |
dc.contributor.author | Kim, So Yeon | ko |
dc.contributor.author | Yi, Hyon-Seung | ko |
dc.contributor.author | Lee, Young-Sun | ko |
dc.contributor.author | Park, Seol-Hee | ko |
dc.contributor.author | Jang, Mi-Jin | ko |
dc.contributor.author | Jo, Eunjung | ko |
dc.contributor.author | Kim, Sun Chang | ko |
dc.contributor.author | Han, Yong-Mahn | ko |
dc.contributor.author | Park, Keun-Gyu | ko |
dc.contributor.author | Jeong, Won-Il | ko |
dc.date.accessioned | 2016-09-07T01:42:13Z | - |
dc.date.available | 2016-09-07T01:42:13Z | - |
dc.date.created | 2016-08-16 | - |
dc.date.created | 2016-08-16 | - |
dc.date.created | 2016-08-16 | - |
dc.date.issued | 2016-08 | - |
dc.identifier.citation | HEPATOLOGY, v.64, no.2, pp.616 - 631 | - |
dc.identifier.issn | 0270-9139 | - |
dc.identifier.uri | http://hdl.handle.net/10203/212551 | - |
dc.description.abstract | During liver injury, hepatocytes secrete exosomes that include diverse types of self-RNAs. Recently, self-noncoding RNA has been recognized as an activator of Toll-like 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-stage liver fibrosis induced by a single or 2-week injection of carbon tetrachloride (CCl4), increased interleukin (IL)-17A production was detected primarily in hepatic gamma delta T cells in wild-type (WT) mice. However, liver fibrosis and IL-17A production by gamma delta T cells were both significantly attenuated in TLR3 knockout (KO) mice compared with WT mice. More interestingly, IL-17A-producing gamma delta T cells were in close contact with activated hepatic stellate cells (HSCs), suggesting a role for HSCs in IL-17A production by gamma delta T cells. In vitro treatments with exosomes derived from CCl4-treated hepatocytes significantly increased the expression of IL-17A, IL-1 beta, and IL-23 in WT HSCs but not in TLR3 KO HSCs. Furthermore, IL-17A production by gamma delta T cells was substantially increased upon coculturing with exosome-treated WT HSCs or conditioned medium from TLR3-activated WT HSCs. However, similar increases were not detected when gamma delta T cells were cocultured with exosome-treated HSCs from IL-17A 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-17A production by gamma delta T cells, as well as liver fibrosis. Conclusion: In liver injury, the exosome-mediated activation of TLR3 in HSCs exacerbates liver fibrosis by enhancing IL-17A production by gamma delta T cells, which might be associated with HSC stimulation by unknown self-TLR3 ligands from damaged hepatocytes. Therefore, TLR3 might be a novel therapeutic target for liver fibrosis | - |
dc.language | English | - |
dc.publisher | WILEY-BLACKWELL | - |
dc.subject | NATURAL-KILLER-CELLS | - |
dc.subject | CARBON-TETRACHLORIDE | - |
dc.subject | HEPATIC INFLAMMATION | - |
dc.subject | KUPFFER CELLS | - |
dc.subject | GROWTH-FACTOR | - |
dc.subject | HELPER-CELLS | - |
dc.subject | MICE | - |
dc.subject | RNA | - |
dc.subject | DIFFERENTIATION | - |
dc.subject | EXPRESSION | - |
dc.title | Exosome-Mediated Activation of Toll-Like Receptor 3 in Stellate Cells Stimulates Interleukin-17 Production by gamma delta T Cells in Liver Fibrosis | - |
dc.type | Article | - |
dc.identifier.wosid | 000380034500029 | - |
dc.identifier.scopusid | 2-s2.0-84978977442 | - |
dc.type.rims | ART | - |
dc.citation.volume | 64 | - |
dc.citation.issue | 2 | - |
dc.citation.beginningpage | 616 | - |
dc.citation.endingpage | 631 | - |
dc.citation.publicationname | HEPATOLOGY | - |
dc.identifier.doi | 10.1002/hep.28644 | - |
dc.contributor.localauthor | Kim, Sun Chang | - |
dc.contributor.localauthor | Han, Yong-Mahn | - |
dc.contributor.localauthor | Jeong, Won-Il | - |
dc.contributor.nonIdAuthor | Yi, Hyon-Seung | - |
dc.contributor.nonIdAuthor | Lee, Young-Sun | - |
dc.contributor.nonIdAuthor | Park, Seol-Hee | - |
dc.contributor.nonIdAuthor | Jang, Mi-Jin | - |
dc.contributor.nonIdAuthor | Jo, Eunjung | - |
dc.contributor.nonIdAuthor | Park, Keun-Gyu | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | NATURAL-KILLER-CELLS | - |
dc.subject.keywordPlus | CARBON-TETRACHLORIDE | - |
dc.subject.keywordPlus | HEPATIC INFLAMMATION | - |
dc.subject.keywordPlus | KUPFFER CELLS | - |
dc.subject.keywordPlus | GROWTH-FACTOR | - |
dc.subject.keywordPlus | HELPER-CELLS | - |
dc.subject.keywordPlus | MICE | - |
dc.subject.keywordPlus | RNA | - |
dc.subject.keywordPlus | DIFFERENTIATION | - |
dc.subject.keywordPlus | EXPRESSION | - |
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