{"created":"2023-07-27T06:58:04.905678+00:00","id":55705,"links":{},"metadata":{"_buckets":{"deposit":"ef99c956-7623-4a35-a9af-33acbfec0526"},"_deposit":{"created_by":18,"id":"55705","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"55705"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00055705","sets":["2812:2813:2833"]},"author_link":["91567","20168"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2002-03-25","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"2p.","bibliographicVolumeNumber":"1998 – 2000","bibliographic_titles":[{"bibliographic_title":"平成12(2000)年度 科学研究費補助金 基盤研究(A) 研究成果報告書概要"},{"bibliographic_title":"2000 Fiscal Year Final Research Report Summary","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":"CD19の発現量がヒトにおいても自己免疫の誘導に関与しているという仮説の下、全身性強皮症(SSc)由来B細胞上のCD19の発現量をフローサイトメトリーにて解析した。SSc由来B細胞上のCD19の発現量は健常人に比して20%増加していた。この20%のCD19発現量の増加が自己免疫を誘導しうるかどうかを、同様に約20%だけCD19の発現量が増加したCD19トランスジェニック(TG)マウスを用いて検討した。このマウスでは抗1本鎖DNA抗体、抗2本鎖DNA抗体、抗ヒストン抗体、リウマトイド因子が野生型マウスに比べ高値であった。さらに抗紡錘体極抗体も30%で検出された。従って、SScにおける20%のCD19発現量の増加が自己免疫を誘導している可能性が示唆された。この事実に基づき、tight skin mouse(Tsk)マウスにCD19の機能を導入した新たなSSc動物モデルの開発、またCD19機能と皮膚硬化の関係を明らかにする目的で、TskマウスにCD19TGマウスおよびCD19ノックアウト(KO)マウスTskマウスを交配して、CD19TG Tskマウス、CD19KO Tskマウスを作成した。CD19TG TskマウスではTskマウスで認められなかったIgG型抗topo 1抗体産生を誘導でき、さらに多様な自己抗体の産生の誘導も認められた。従って、CD19TG Tskマウスは従来のどのSSc動物モデルよりもヒトSScの免疫学的特徴をより正確に反映していた。CD19TG TskマウスではTskマウスと比較して皮膚硬化の増強が認められなかったものの、Tskマウスで認められた自己免疫および免疫異常がほぼ除去されたCD19KO Tskマウスでは、Tskマウスと比較して皮膚硬化が著明に減弱したことから、CD19発現は皮膚硬化の誘導にも重要な役割を担っていることが示唆された。","subitem_description_type":"Abstract"},{"subitem_description":"CD19 regulates intrinsic B lymphocyte signaling thresholds. To determine a role of CD19 expression in autoantibody production, we have assessed autoimmunity in a transgenic mice (CD19TG) with subtle 15-29% CD19 increases. Various autoantibodies were produced in CD19TG mice, demonstrating that small changes in CD19 expression can induce autoantibody production. Similar changes in CD19 expression were found on B cells from patients with systemic sclerosis (SSc). CD19 density on blood B cells from SSc patients was significantly (〜20%) higher compared with normal individuals, while CD20, CD22, and CD40 expression were normal. These results suggest that modest changes in the expression or function of CD19 may shift the balance between tolerance and immunity to autoimmunity.\nTight skin (Tsk) mice overall reflect the skin sclerosis in human SSc, but do not precisely mimic the immunologic abnormalities in human SSc. Based upon the results described above, we chose the immunologic function of CD19 for the development of new mouse model of SSc. Tsk mice were mated with CD19TG mice that overexpress CD19 by 2.6-fold or CD19 knock-out (KO) mice to generate CD19TG Tsk or CD19KO Tsk mice. In CD19TG Tsk mice, IgG anti-topoisomerase I antibody levels were elevated compared with wild-type mice, which was not observed in Tsk mice. Furthermore, the production of various autoantibodies was induced in CD19TG mice. This suggests that CD19TG Tsk mice would be the SSc animal model that most precisely reflect immunologic abnormalities in human SSc. However, skin sclerosis in CD19TG Tsk mice did not increase compared with Tsk mice. In contrast, the development of skin sclerosis was significantly inhibited in CD19KO Tsk mice in which the various immunologic abnormalities were almost completely abolished. Thus, expression and function of CD19 may also play a critical role in the development of skin sclerosis in Tsk mice.","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:10357008, 研究期間(年度):1998 – 2000","subitem_description_type":"Other"},{"subitem_description":"出典：「CD19,CD22の免疫学的機能を応用した全身性強皮症の新しい動物モデルの開発」研究成果報告書　課題番号10357008\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（https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-10357008/103570082000kenkyu_seika_hokoku_gaiyo/ ）を加工して作成","subitem_description_type":"Other"}]},"item_9_description_5":{"attribute_name":"提供者所属","attribute_value_mlt":[{"subitem_description":"金沢大学附属病院","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00061980","subitem_identifier_reg_type":"JaLC"}]},"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=20215792"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=20215792","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10357008/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10357008/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-10357008/103570082000kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-10357008/103570082000kenkyu_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":"2021-12-03"}],"displaytype":"detail","filename":"HO-PR-SATO-S-kaken 2002-2p.pdf","filesize":[{"value":"90.9 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"HO-PR-SATO-S-kaken 2002-2p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/55705/files/HO-PR-SATO-S-kaken 2002-2p.pdf"},"version_id":"22fd4b0e-36ab-46ac-8cf7-4b5f9cf71760"}]},"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":"CD19,CD22の免疫学的機能を応用した全身性強皮症の新しい動物モデルの開発","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"CD19,CD22の免疫学的機能を応用した全身性強皮症の新しい動物モデルの開発"},{"subitem_title":"Development of the new animal model for systemic sclerosis using the immunologic function of CD19 and CD22","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2833"],"pubdate":{"attribute_name":"公開日","attribute_value":"2021-12-03"},"publish_date":"2021-12-03","publish_status":"0","recid":"55705","relation_version_is_last":true,"title":["CD19,CD22の免疫学的機能を応用した全身性強皮症の新しい動物モデルの開発"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:06:00.367292+00:00"}