Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 서원효 | * |
dc.date.accessioned | 2021-08-12T16:31:01Z | - |
dc.date.available | 2021-08-12T16:31:01Z | - |
dc.date.issued | 2020 | * |
dc.identifier.issn | 0270-9139 | * |
dc.identifier.issn | 1527-3350 | * |
dc.identifier.other | OAK-29974 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/258622 | - |
dc.description.abstract | Background and Aims Mitochondrial double-stranded RNA (mtdsRNA) and its innate immune responses have been reported previously; however, mtdsRNA generation and its effects on alcohol-associated liver disease (ALD) remain unclear. Here, we report that hepatic mtdsRNA stimulates toll-like receptor 3 (TLR3) in Kupffer cells through the exosome (Exo) to enhance interleukin (IL)-17A (IL-17A) production in ALD. Approach and Results Following binge ethanol (EtOH) drinking, IL-17A production primarily increased in gamma delta T cells of wild-type (WT) mice, whereas the production of IL-17A was mainly facilitated by CD4(+) T cells in acute-on-chronic EtOH consumption. These were not observed in TLR3 knockout (KO) or Kupffer cell-depleted WT mice. The expression of polynucleotide phosphorylase, an mtdsRNA-restricting enzyme, was significantly decreased in EtOH-exposed livers and hepatocytes of WT mice. Immunostaining revealed that mtdsRNA colocalized with the mitochondria in EtOH-treated hepatocytes from WT mice and healthy humans. Bioanalyzer analysis revealed that small-sized RNAs were enriched in EtOH-treated Exos (EtOH-Exos) rather than EtOH-treated microvesicles in hepatocytes of WT mice and humans. Quantitative real-time PCR and RNA sequencing analyses indicated that mRNA expression of mitochondrial genes encoded by heavy and light strands was robustly increased in EtOH-Exos from mice and humans. After direct treatment with EtOH-Exos, IL-1 beta expression was significantly increased in WT Kupffer cells but not in TLR3 KO Kupffer cells, augmenting IL-17A production of gamma delta T cells in mice and humans. Conclusions EtOH-mediated generation of mtdsRNA contributes to TLR3 activation in Kupffer cells through exosomal delivery. Consequently, increased IL-1 beta expression in Kupffer cells triggers IL-17A production in gamma delta T cells at the early stage that may accelerate IL-17A expression in CD4(+) T cells in the later stage of ALD. Therefore, mtdsRNA and TLR3 may function as therapeutic targets in ALD. | * |
dc.language | English | * |
dc.publisher | WILEY | * |
dc.title | Mitochondrial Double-Stranded RNA in Exosome Promotes Interleukin-17 Production Through Toll-Like Receptor 3 in Alcohol-associated Liver Injury | * |
dc.type | Article | * |
dc.relation.issue | 2 | * |
dc.relation.volume | 72 | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.startpage | 609 | * |
dc.relation.lastpage | 625 | * |
dc.relation.journaltitle | HEPATOLOGY | * |
dc.identifier.doi | 10.1002/hep.31041 | * |
dc.identifier.wosid | WOS:000530993500001 | * |
dc.author.google | Lee, Jun-Hee | * |
dc.author.google | Shim, Young-Ri | * |
dc.author.google | Seo, Wonhyo | * |
dc.author.google | Kim, Myung-Ho | * |
dc.author.google | Choi, Won-Mook | * |
dc.author.google | Kim, Hee-Hoon | * |
dc.author.google | Kim, Ye Eun | * |
dc.author.google | Yang, Keungmo | * |
dc.author.google | Ryu, Tom | * |
dc.author.google | Jeong, Jong-Min | * |
dc.author.google | Choi, Hei-Gwon | * |
dc.author.google | Eun, Hyuk Soo | * |
dc.author.google | Kim, Seok-Hwan | * |
dc.author.google | Mun, Hyejin | * |
dc.author.google | Yoon, Je-Hyun | * |
dc.author.google | Jeong, Won-Il | * |
dc.contributor.scopusid | 서원효(56335935100) | * |
dc.date.modifydate | 20240315114146 | * |