{"created":"2023-07-27T06:55:00.139809+00:00","id":50618,"links":{},"metadata":{"_buckets":{"deposit":"5a9b4cc8-69db-4730-ad77-4cb98f603dde"},"_deposit":{"created_by":18,"id":"50618","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"50618"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00050618","sets":["2812:2813:2826"]},"author_link":["304","91641"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2008-03","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"3p.","bibliographicVolumeNumber":"2006-2007","bibliographic_titles":[{"bibliographic_title":"平成19(2007)年度 科学研究費補助金 基盤研究(C) 研究成果報告書"},{"bibliographic_title":"2007 Fiscal Year Final Research Report","bibliographic_titleLang":"en"}]}]},"item_9_creator_33":{"attribute_name":"著者別表示","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{}],"nameIdentifiers":[{},{}]}]},"item_9_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"全身性強皮症は、皮膚や内臓臓器の線維化を特徴とする膠原病であるが、皮膚の線維化に著効する薬剤はみられない。これまでに我々は、強皮症の病態において、B細胞が重要な役割を果たしている可能性について発表してきた。\n今回、強皮症の遺伝的なモデルであるtight skin mouse(TSKマウス)に、B細胞を除去可能な抗CD20抗体を新生仔期より皮下注射投与した場合には、骨髄や末梢のB細胞が長期に消失し、皮膚硬化の進行が43%まで抑制された。また、TSKマウスにみられる自己抗体の産生もみられなくなった。一方で、一旦皮膚硬化や自己抗体産生が完成した大人のマウスでは十分な効果がみられなかった。\nB細胞除去療法がTSKマウスの皮膚硬化を抑制した機序として検討結果から想定されるのは、TSKマウスにみられるB細胞の機能異常がB細胞除去により消失し、これにより皮膚に浸潤するT細胞やマクロファージからのサイトカイン産生が野生型レベルに是正されたためと考えられた。\n以上の結果から、TSKマウスの皮膚硬化の出現には何らかのB細胞機能異常が関与していると考えられ、抗CD20抗体治療は皮膚のサイトカインの発現を制御することにより、皮膚硬化の進行を抑制することが明らかとなった。また、抗CD20抗体は自己抗体を産生する形質細胞へのB細胞の分化を抑制することにより、TSKマウスにみられる自己免疫異常を抑制することも明らかとなった。\n以上の結果は、ヒトの全身性強皮症においても発症早期の抗CD20抗体治療が有効である可能性を示唆しており、本研究の成果は実際の臨床応用にも役立つものと思われた。","subitem_description_type":"Abstract"},{"subitem_description":"Systemic sclerosis (scleroderma) is an autoimmune disease characterized by excessive extracellular matrix deposition in the skin. Although autoantibody production correlates with skin sclerosis, a direct role for B lymphocytes in disease development or progression has remained controversial. To address this issue, skin sclerosis and autoimmunity was assessed in tight-skin mice, a genetic model of human systemic sclerosis, following circulating and tissue B cell depletion using an anti-mouse CD20 mAb before and after disease development. CD20 mAb treatment (10-20 rig) depleted the majority (85-99%) of circulating and tissue B cells in newborn and adult tight-skin mice. Dose-dependent B cell depletion in newborn tight-skin mice significantly suppressed (-43%) the development of skin fibrosis and hypergammaglobulinemia, and abrogated rheumatoid factor and autoantibody production. B cell depletion in young tight-skin mice also restored a more normal balance between Th1 and Th2 cytokine mRNA expression in the skin and spleen. By contrast, effective B cell depletion did not affect skin fibrosis, hypergammaglobulinemia, rheumatoid factor and autoantibody levels in adult mice with established disease. Thereby, B cell depletion during disease onset suppressed skin fibrosis, indicating that B cells contribute to the initiation of systemic sclerosis pathogenesis in tight-skin mice but are not required for disease maintenance.","subitem_description_type":"Abstract"}]},"item_9_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究課題/領域番号:18591238, 研究期間(年度):2006-2007","subitem_description_type":"Other"},{"subitem_description":"出典：「B細胞除去療法による強皮症モデルマウスの治療」研究成果報告書　課題番号18591238\n  (KAKEN：科学研究費助成事業データベース（国立情報学研究所）)\n　　　本文データは著者版報告書より作成","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00056927","subitem_identifier_reg_type":"JaLC"}]},"item_9_publisher_17":{"attribute_name":"公開者","attribute_value_mlt":[{"subitem_publisher":"金沢大学附属病院"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/search/?qm=50283130"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=50283130","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591238/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591238/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-18591238/185912382007kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-18591238/185912382007kenkyu_seika_hokoku_gaiyo/","subitem_relation_type_select":"URI"}}]},"item_9_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-02-10"}],"displaytype":"detail","filename":"ME-PR-HASEGAWA-M-kaken 2008-3p.pdf","filesize":[{"value":"109.3 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"ME-PR-HASEGAWA-M-kaken 2008-3p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/50618/files/ME-PR-HASEGAWA-M-kaken 2008-3p.pdf"},"version_id":"2c2d35b9-1a5c-417f-9104-58c7823826e9"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"B細胞除去療法による強皮症モデルマウスの治療","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"B細胞除去療法による強皮症モデルマウスの治療"},{"subitem_title":"B cell depletion therapy for the model mouse of scleroderma","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2826"],"pubdate":{"attribute_name":"公開日","attribute_value":"2020-02-10"},"publish_date":"2020-02-10","publish_status":"0","recid":"50618","relation_version_is_last":true,"title":["B細胞除去療法による強皮症モデルマウスの治療"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:23:47.257794+00:00"}