DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Jeong, Won-il | - |
dc.contributor.advisor | 정원일 | - |
dc.contributor.author | Seo, Wonhyo | - |
dc.contributor.author | 서원효 | - |
dc.date.accessioned | 2017-03-29T02:47:36Z | - |
dc.date.available | 2017-03-29T02:47:36Z | - |
dc.date.issued | 2016 | - |
dc.identifier.uri | http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=648222&flag=dissertation | en_US |
dc.identifier.uri | http://hdl.handle.net/10203/222281 | - |
dc.description | 학위논문(박사) - 한국과학기술원 : 의과학학제전공, 2016.2 ,[vi, 79 p. :] | - |
dc.description.abstract | During liver injury, damaged hepatocytes are able to release 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 hepatocyte-derived exosomes and the activation of TLR3 are not yet fully understood in the pathogenesis of liver fibrosis. Following acute liver injury and early-stage liver fibrosis induced by a single or 2-week injection of carbon tetrachloride $(CCl_4)$, increased interleukin-17A (IL-17A) production was mainly detected in hepatic γδ T cells in wild-type (WT) mice. However, the degree of liver fibrosis and IL-17A production by γδ T cells were both significantly attenuated in TLR3 KO mice compared with WT mice. More interestingly, IL-17A-producing γδ T cells were in close contact with activated hepatic stellate cells (HSCs), suggesting an interaction between HSCs and γδ T cells. In vitro treatments with exosomes derived from $CCl_4-treated$ hepatocytes significantly increased the expression of IL-17A, IL-1β, and IL-23 in WT HSCs but not in TLR3 KO HSCs. Furthermore, IL-17A production by γδ T cells was substantially increased upon co-culturing with exosome-treated WT HSCs or conditioned medium from TLR3-activated WT HSCs. However, similar increases were not detected when γδ T cells were co-cultured with exosome-treated HSCs from IL-17A KO or TLR3 KO mice. Using reciprocal bone marrow transplantation between WT and TLR3 KO mice, we demonstrated that TLR3 deficiency in HSCs contributed to decreased IL-17A production by γδ T cells, as well as liver fibrosis. In liver injury, the exosome-mediated activation of TLR3 in HSCs exacerbates liver fibrosis by enhancing IL-17A production by γδ 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 | eng | - |
dc.publisher | 한국과학기술원 | - |
dc.subject | RNA | - |
dc.subject | self-ligand | - |
dc.subject | IL-1β | - |
dc.subject | IL-23 | - |
dc.subject | RORγt | - |
dc.subject | 간섬유화 | - |
dc.subject | 간성상세포 | - |
dc.subject | 엑소좀 | - |
dc.subject | 톨유사수용체 | - |
dc.subject | 감마델타 T 세포 | - |
dc.title | (The) role of exosome-mediated activation of toll-like receptor 3 in hepatic stellate cells during liver fibrogenesis | - |
dc.title.alternative | 간섬유화 과정에서 exosome 매개 toll-like receptor 3 활성화를 통한 간성상세포의 역할에 관한 연구 | - |
dc.type | Thesis(Ph.D) | - |
dc.identifier.CNRN | 325007 | - |
dc.description.department | 한국과학기술원 :의과학학제전공, | - |
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