https://scholars.lib.ntu.edu.tw/handle/123456789/507630
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | Wu S.-J. | en_US |
dc.contributor.author | YAO-HSU YANG | en_US |
dc.contributor.author | Tsuneyama K. | en_US |
dc.contributor.author | Leung P.S. | en_US |
dc.contributor.author | Illarionov P. | en_US |
dc.contributor.author | Gershwin M.E. | en_US |
dc.contributor.author | YA-HUI CHUANG | en_US |
dc.creator | Wu S.-J. ;Yang Y.-H. ;Tsuneyama K. ;Leung P.S. ;Illarionov P. ;Gershwin M.E. ;Ya-Hui Chuang | - |
dc.date.accessioned | 2020-07-01T06:55:03Z | - |
dc.date.available | 2020-07-01T06:55:03Z | - |
dc.date.issued | 2011 | - |
dc.identifier.issn | 0270-9139 | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/507630 | - |
dc.description.abstract | Murine models of autoimmunity allow the study of the earliest events in disease pathogenesis. Our laboratory has developed a xenobiotic induced model of primary biliary cirrhosis (PBC) following immunization of mice with 2-octynoic acid coupled to bovine serum albumin (2-OA-BSA), an antigen selected following quantitative structure-activity relationship analysis of the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2), the immunodominant autoantigen of PBC. Recent data in humans with PBC has suggested that a major component of liver pathology is due to activation of innate immunity. We took advantage of our 2-OA-BSA model and immunized mice with and without the addition of α-galactosylceramide (α-GalCer), an invariant natural killer T cell activator. Importantly, we report herein that 2-OA-BSA-immunized mice exposed to α-GalCer develop a profound exacerbation of their autoimmune cholangitis, including significant increases in CD8+ T-cell infiltrates, portal inflammation, granuloma formation, and bile duct damage. Furthermore, such mice produce increased levels of antimitochondrial antibodies and have evidence of fibrosis, a feature not previously reported in the murine models of PBC. Conclusion: Our data suggests a primary role of innate immunity in the exacerbation of autoimmune cholangitis and also become a logical explanation for the recurrence of PBC following liver transplantation in the absence of major histocompatability complex compatibility. We submit that PBC begins with loss of tolerance to PDC-E2 and a multilineage antimitochondrial response in which autoreactive CD8+ T cells are critical. However, the perpetuation of disease and its exacerbation will also be modulated by innate immune mechanisms. ? 2010 American Association for the Study of Liver Diseases. | - |
dc.relation.ispartof | Hepatology | - |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | 2 octynoic acid; alpha galactosylceramide; autoantigen; bovine serum albumin; mitochondrion antibody; octanoic acid; pyruvate dehydrogenase complex; pyruvate dehydrogenase complex E2 subunit; unclassified drug; animal cell; animal experiment; animal model; animal tissue; article; autoimmune cholangitis; autoimmunity; bile duct injury; biliary tract fibrosis; CD8+ T lymphocyte; cholangitis; controlled study; disease exacerbation; female; flow cytometry; histopathology; immunomodulation; immunopathogenesis; innate immunity; lymphocytic infiltration; mouse; natural killer T cell; nonhuman; primary biliary cirrhosis; priority journal; quantitative structure activity relation; T lymphocyte activation; Animals; Autoimmune Diseases; Cholangitis; Disease Models, Animal; Fatty Acids, Monounsaturated; Female; Immunity, Innate; Liver Cirrhosis; Liver Cirrhosis, Biliary; Mice; Mice, Inbred C57BL; Mitochondria, Liver; Natural Killer T-Cells | - |
dc.title | Innate immunity and primary biliary cirrhosis: Activated invariant natural killer T cells exacerbate murine autoimmune cholangitis and fibrosis | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.1002/hep.24113 | - |
dc.identifier.pmid | 21374662 | - |
dc.identifier.scopus | 2-s2.0-79952223723 | - |
dc.relation.pages | 915-925 | - |
dc.relation.journalvolume | 53 | - |
dc.relation.journalissue | 3 | - |
item.cerifentitytype | Publications | - |
item.fulltext | no fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.openairetype | journal article | - |
item.grantfulltext | none | - |
crisitem.author.dept | Pediatrics | - |
crisitem.author.dept | Pediatrics-NTUH | - |
crisitem.author.dept | Clinical Laboratory Sciences and Medical Biotechnology | - |
crisitem.author.orcid | 0000-0002-6266-9864 | - |
crisitem.author.orcid | 0000-0003-0857-0035 | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
顯示於: | 醫學檢驗暨生物技術學系 |
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