{"created":"2023-07-27T06:28:32.701919+00:00","id":13141,"links":{},"metadata":{"_buckets":{"deposit":"ef79e822-96a3-4fdc-9ec6-32368fe1df32"},"_deposit":{"created_by":3,"id":"13141","owners":[3],"pid":{"revision_id":0,"type":"depid","value":"13141"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00013141","sets":["1132:1133:1134"]},"author_link":["143","20910","450","20218","20449","20168","20911","20912","20909","304"],"item_4_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2002-01-01","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"11","bibliographicPageEnd":"1462","bibliographicPageStart":"1453","bibliographicVolumeNumber":"109","bibliographic_titles":[{"bibliographic_title":"Journal of Clinical Investigation"}]}]},"item_4_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"The tight-skin (TSK/+) mouse, a genetic model for human systemic sclerosis (SSc), develops cutaneous fibrosis and autoantibodies against SSc-specific target autoantigens. Although molecular mechanisms explaining the development of fibrosis and autoimmunity in SSc patients or TSK/+ mice remain unknown, we recently demonstrated that SSc patients overexpress CD19, an important regulatory molecule expressed by B lymphocytes. B cells from CD19-deficient mice are hyporesponsive to transmembrane signals, while B cells overexpressing CD19 are hyperresponsive and generate autoantibodies. In this study, TSK/+ B cells also exhibited a hyperresponsive phenotype with decreased surface IgM expression, enhanced serum Ig production, and spontaneous autoantibody production. Moreover, CD19 tyrosine phosphorylation was constitutively augmented in TSK/+ B cells. CD19-mediated [Ca2+]i responses, Vav phosphorylation, and Lyn kinase activity were similarly enhanced. Studies of TSK/+ mice deficient in CD19 expression demonstrated that CD19 deficiency significantly decreased skin fibrosis in TSK/+ mice. Additionally, CD19 loss in TSK/+ mice upregulated surface IgM expression and completely abrogated hyper-γ-globulinemia and autoantibody production. CD19 deficiency also inhibited IL-6 production by TSK/+ B cells. Thus, chronic B cell activation resulting from augmented CD19 signaling in TSK/+ mice leads to skin sclerosis possibly through IL-6 overproduction as well as autoimmunity.","subitem_description_type":"Abstract"}]},"item_4_description_5":{"attribute_name":"提供者所属","attribute_value_mlt":[{"subitem_description":"金沢大学大学院医学系研究科血管分子科学","subitem_description_type":"Other"}]},"item_4_publisher_17":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"American Society for Clinical Investigation"}]},"item_4_relation_12":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1172/JCI200215078","subitem_relation_type_select":"DOI"}}]},"item_4_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0021-9738","subitem_source_identifier_type":"ISSN"}]},"item_4_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Saito, Eriko"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Fujimoto, Manabu"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"Hasegawa, Minoru"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"Komura, Kazuhiro"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"Hamaguchi, Yasuhito"}],"nameIdentifiers":[{},{},{},{}]},{"creatorNames":[{"creatorName":"Kaburagi, Yuko"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Nagao, Tetsuya"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Takehara, Kazuhiko"}],"nameIdentifiers":[{},{},{},{}]},{"creatorNames":[{"creatorName":"Tedder, Thomas F."}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Sato, Shinichi"}],"nameIdentifiers":[{},{},{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2017-10-03"}],"displaytype":"detail","filename":"ME-PR-FUJIMOTO-M-1453.pdf","filesize":[{"value":"1.3 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"ME-PR-FUJIMOTO-M-1453.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/13141/files/ME-PR-FUJIMOTO-M-1453.pdf"},"version_id":"e8081595-7ba8-4c5f-be9e-ab55726beb08"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"CD19-dependent B lymphocyte signaling thresholds influence skin fibrosis and autoimmunity in the tight-skin mouse","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"CD19-dependent B lymphocyte signaling thresholds influence skin fibrosis and autoimmunity in the tight-skin mouse"}]},"item_type_id":"4","owner":"3","path":["1134"],"pubdate":{"attribute_name":"公開日","attribute_value":"2017-10-03"},"publish_date":"2017-10-03","publish_status":"0","recid":"13141","relation_version_is_last":true,"title":["CD19-dependent B lymphocyte signaling thresholds influence skin fibrosis and autoimmunity in the tight-skin mouse"],"weko_creator_id":"3","weko_shared_id":-1},"updated":"2023-07-28T01:10:02.085324+00:00"}