{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T08:22:05Z","timestamp":1743063725860},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2012,4,20]],"date-time":"2012-04-20T00:00:00Z","timestamp":1334880000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,4,20]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>One of the major obstacles in dissecting the mechanism of pathology in human primary biliary cirrhosis (PBC) has been the absence of animal models. Our laboratory has focused on a model in which mice, following immunization with a xenobiotic chemical mimic of the immunodominant autoepitope of the E2 component of pyruvate dehydrogenase complex (PDC-E2), develop autoimmune cholangitis. In particular, following immunization with 2-octynoic acid (a synthetic chemical mimic of lipoic acid-lysine located within the inner domain of PDC-E2) coupled to bovine serum albumin (BSA), several strains of mice develop typical anti-mitochondrial autoantibodies and portal inflammation. The role of innate immune effector cells, such as natural killer (NK) cells and that NK\u2003T cells, was studied in this model based on the hypothesis that early events during immunization play an important role in the breakdown of tolerance. We report herein that, following in-vivo depletion of NK and NK\u2003T cells, there is a marked suppression of anti-mitochondrial autoantibodies and cytokine production from autoreactive T cells. However, there was no change in the clinical pathology of portal inflammation compared to controls. These data support the hypothesis that there are probably multiple steps in the natural history of PBC, including a role of NK and NK\u2003T cells in initiating the breakdown of tolerance. However, the data suggest that adaptive autoimmune effector mechanisms are required for the progression of clinical disease.<\/jats:p>","DOI":"10.1111\/j.1365-2249.2012.04581.x","type":"journal-article","created":{"date-parts":[[2012,3,5]],"date-time":"2012-03-05T15:19:15Z","timestamp":1330960755000},"page":"279-284","source":"Crossref","is-referenced-by-count":22,"title":["The role of natural killer (NK) and NK\u2003T cells in the loss of tolerance in murine primary biliary cirrhosis"],"prefix":"10.1093","volume":"168","author":[{"given":"S","family":"Shimoda","sequence":"first","affiliation":[{"name":"Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Tsuneyama","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"Fourth Department of Internal Medicine, Teikyo University School of Medicine, Kanagawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Harada","sequence":"additional","affiliation":[{"name":"Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y","family":"Nakanuma","sequence":"additional","affiliation":[{"name":"Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center, Kubara, Omura, Nagasaki, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Ishibashi","sequence":"additional","affiliation":[{"name":"Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center, Kubara, Omura, Nagasaki, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Hisamoto","sequence":"additional","affiliation":[{"name":"Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Niiro","sequence":"additional","affiliation":[{"name":"Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P S C","family":"Leung","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy and Clinical Immunology, School of Medicine, University of California Davis, Davis, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A A","family":"Ansari","sequence":"additional","affiliation":[{"name":"Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M E","family":"Gershwin","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy and Clinical Immunology, School of Medicine, University of California Davis, Davis, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Akashi","sequence":"additional","affiliation":[{"name":"Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2012,4,20]]},"reference":[{"key":"2021122708381629700_b1","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1056\/NEJMra043898","article-title":"Primary biliary 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