{"created":"2025-08-25T02:00:06.200168+00:00","id":2000516,"links":{},"metadata":{"_buckets":{"deposit":"48dc21bd-e7f8-4e03-91c9-4fbd3757eb7a"},"_deposit":{"created_by":4,"id":"2000516","owner":"4","owners":[4],"pid":{"revision_id":0,"type":"depid","value":"2000516"},"status":"published"},"_oai":{"id":"oai:hama-med.repo.nii.ac.jp:02000516","sets":["2:15:17"]},"author_link":[],"control_number":"2000516","item_1747115756369":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"36996700","subitem_relation_type_select":"PMID"}}]},"item_1747115938917":{"attribute_name":"出版社DOI","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1016/j.jaut.2023.103027","subitem_relation_type_select":"DOI"}}]},"item_1747116992798":{"attribute_name":"NII書誌ID","attribute_value_mlt":[{"subitem_source_identifier":"AA10717368","subitem_source_identifier_type":"NCID"}]},"item_1747119187110":{"attribute_name":"学位の区分","attribute_value_mlt":[{"subitem_description":"doctoral","subitem_description_language":"en","subitem_description_type":"Other"}]},"item_1747119200876":{"attribute_name":"学位の分野","attribute_value_mlt":[{"subitem_description":"医学系研究科","subitem_description_language":"ja","subitem_description_type":"Other"}]},"item_1748498410707":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_1749433886912":{"attribute_name":"EISSN","attribute_value_mlt":[{"subitem_source_identifier":"1095-9157","subitem_source_identifier_type":"EISSN"}]},"item_1751527345221":{"attribute_name":"要旨⇔論文へのリンク","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_language":"ja","subitem_relation_name_text":"学位論文要旨"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"http://hdl.handle.net/10271/0002000248","subitem_relation_type_select":"HDL"}}]},"item_30001_access_rights4":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_30001_alternative_title1":{"attribute_name":"その他のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"免疫寛容破綻と胆汁酸負荷：原発性胆汁性胆管炎の免疫病態と自然経過における難問を解決する","subitem_alternative_title_language":"ja"}]},"item_30001_bibliographic_information17":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2023-03-28","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"103027","bibliographicVolumeNumber":"136","bibliographic_titles":[{"bibliographic_title":"Journal of Autoimmunity","bibliographic_titleLang":"en"}]}]},"item_30001_creator2":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorAffiliations":[{"affiliationNameIdentifiers":[{"affiliationNameIdentifier":"0000000089376696","affiliationNameIdentifierScheme":"ISNI","affiliationNameIdentifierURI":"https://isni.org/isni/0000000089376696"},{"affiliationNameIdentifier":"00ndx3g44","affiliationNameIdentifierScheme":"ROR","affiliationNameIdentifierURI":"https://ror.org/00ndx3g44"}],"affiliationNames":[{"affiliationName":"浜松医科大学","affiliationNameLang":"ja"},{"affiliationName":"ハママツイカダイガク","affiliationNameLang":"ja-Kana"},{"affiliationName":"Hamamatsu University School of Medicine","affiliationNameLang":"en"}]}],"creatorNames":[{"creatorName":"山下, 真帆","creatorNameLang":"ja","creatorNameType":"Personal"},{"creatorName":"ヤマシタ, マホ","creatorNameLang":"ja-Kana","creatorNameType":"Personal"},{"creatorName":"Yamashita, Maho","creatorNameLang":"en","creatorNameType":"Personal"}]}]},"item_30001_date_granted20":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2024-09-20"}]},"item_30001_degree_grantor21":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"浜松医科大学"},{"subitem_degreegrantor_language":"en","subitem_degreegrantor_name":"Hamamatsu University School of Medicine"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"13802","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_30001_degree_name19":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（医学）","subitem_degreename_language":"ja"}]},"item_30001_description8":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Primary biliary cholangitis (PBC) is a classic autoimmune disease due to the loss of tolerance to self-antigens. Bile acids (BA) reportedly play a major role in biliary inflammation and/or in the modulation of dysregulated immune responses in PBC. Several murine models have indicated that molecular mimicry plays a role in autoimmune cholangitis; however, they have all been limited by the relative failure to develop hepatic fibrosis. We hypothesized that species-specific differences in the BA composition between mice and humans were the primary reason for this limited pathology. Here, we aimed to study the impact of human-like hydrophobic BA composition on the development of autoimmune cholangitis and hepatic fibrosis. We took advantage of a unique construct, Cyp2c70/Cyp2a12 double knockout (DKO) mice, which have human-like BA composition, and immunized them with a well-defined mimic of the major mitochondrial autoantigen of PBC, namely 2-octynoic acid (2OA). 2OA-treated DKO mice were significantly exacerbated portal inflammation and bile duct damage with increased Th1 cytokines/chemokines at 8 weeks post-initial immunization. Most importantly, there was clear progression of hepatic fibrosis and increased expression of hepatic fibrosis-related genes. Interestingly, these mice demonstrated increased serum BA concentrations and decreased biliary BA concentrations; hepatic BA levels did not increase because of the upregulation of transporters responsible for the basolateral efflux of BA. Furthermore, cholangitis and hepatic fibrosis were more advanced at 24 weeks post-initial immunization. These results indicate that both the loss of tolerance and the effect of hydrophobic BA are essential for the progression of PBC.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_30001_dissertation_number18":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第995号"}]},"item_30001_file22":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2025-08-25"}],"displaytype":"detail","filename":"DT_995ronbun.pdf","filesize":[{"value":"10.9 MB"}],"format":"application/pdf","mimetype":"application/pdf","url":{"label":"論文本文","objectType":"fulltext","url":"https://hama-med.repo.nii.ac.jp/record/2000516/files/DT_995ronbun.pdf"},"version_id":"2c92360a-67c7-48c8-9191-cefb9f6e0361"}]},"item_30001_language10":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_30001_publisher9":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Elsevier","subitem_publisher_language":"en"}]},"item_30001_rights5":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"Copyright 2023 Elsevier Ltd.","subitem_rights_language":"en"}]},"item_30001_source_identifier16":{"attribute_name":"PISSN","attribute_value_mlt":[{"subitem_source_identifier":"0896-8411","subitem_source_identifier_type":"PISSN"}]},"item_30001_subject7":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Primary biliary cholangitis","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Mouse model","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Bile acids","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Fibrosis","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Chenodeoxycholic acid","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_30001_title0":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Breach of tolerance versus burden of bile acids: Resolving the conundrum in the immunopathogenesis and natural history of primary biliary cholangitis","subitem_title_language":"en"}]},"item_30001_version_type12":{"attribute_name":"出版タイプ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_title":"Breach of tolerance versus burden of bile acids: Resolving the conundrum in the immunopathogenesis and natural history of primary biliary cholangitis","item_type_id":"40002","owner":"4","path":["17"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2025-09-09"},"publish_date":"2025-09-09","publish_status":"0","recid":"2000516","relation_version_is_last":true,"title":["Breach of tolerance versus burden of bile acids: Resolving the conundrum in the immunopathogenesis and natural history of primary biliary cholangitis"],"weko_creator_id":"4","weko_shared_id":-1},"updated":"2025-09-26T00:24:18.784438+00:00"}