PUVA処理制御性樹状細胞による移植片対宿主病への新たな治療戦略

Material type: 文書・図像類

Author: 前馬, 秀昭ほか

Publisher: 金沢大学附属病院小児科

Publication date: 2013-06-19

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Note (General)：: PUVA処理で樹状細胞が制御性樹状細胞の性質を獲得した。その性質が、どのような機序で獲得したか検討した。トリプトファン代謝による細胞増殖の抑制をみるため、indoleamine 2,3-dioxygenase (IDO)の発現を定量PCR法にて測定したところ、樹状細胞のPUVA処理にて5倍以上の発現...

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https://kaken.nii.ac.jp/search/?qm=10419335

https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23791213/

https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-23791213/23791213seika/

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Material Type: 文書・図像類
Title: PUVA処理制御性樹状細胞による移植片対宿主病への新たな治療戦略
Author/Editor: 前馬, 秀昭
Maeba, Hideaki
Author Heading: 前馬, 秀昭
Maeba, Hideaki
Publication, Distribution, etc.: 金沢大学附属病院小児科
Publication Date: 2013-06-19
Publication Date (W3CDTF): 2013-06-19
Alternative Title: New treatment strategy for GVHD by infusion of PUVA-treated-tolerogenic-dendritic cells
Periodical title: 平成24(2012)年度科学研究費補助金若手研究(B) 研究成果報告書 = 2012 Fiscal Year Final Research Report
No. or year of volume/issue: 2011-2012
Volume: 2011-2012
Pages: 4p.-
Text Language Code: jpn
Subject Heading: GVHD
制御性樹状細胞
造血幹細胞移植
PUVA療法
Target Audience: 一般
Note (General): PUVA処理で樹状細胞が制御性樹状細胞の性質を獲得した。その性質が、どのような機序で獲得したか検討した。トリプトファン代謝による細胞増殖の抑制をみるため、indoleamine 2,3-dioxygenase (IDO)の発現を定量PCR法にて測定したところ、樹状細胞のPUVA処理にて5倍以上の発現増加を認めた。PUVA処理が樹状細胞以外の他の血球、リンパ球(CD4、CD8、B220)にもその作用が及ぶか検討した。PUVA処理したリンパ球(CD4、CD8、B220)およびPUVA処理した樹状細胞と同系統の骨髄由来樹状細胞をstimulatorとして、混合リンパ球反応(MLR)を行った。結果、PUVA処理した樹状細胞とともにMLRを施行した群のみ、その反応は抑えられた。体外で樹状細胞を培養し、それにPUVA療法を施行して、体内に輸注する細胞療法がGVHDに対して有効な治療法となりうる可能性が示唆された。
Extracorporeal photopheresis (ECP) is a leukapheresis-based immunomodulatory therapy by exposing isolated white blood cells to photoactive 8-MOP (psoralen) and UVA radiation (PUVA) for refractory acute and chronic graft-versus-host disease (GVHD). We have reported that bone marrow-derived dendritic cells (BM-DCs), which are generated from bone marrow cells plus GM-CSF, acquired tolerogenicity by PUVA-treatment in mice. To clarify the mechanisms of how PUVA-treated DCs induce tolerogenicity in further detail, we compared the expression of the indoleamine 2,3-dioxygenase (IDO), which induces T-cell anergy by tryptophan depletion and by the production of metabolic byproducts collectively known as kynurenines, by real-time PCR between PUVA-DCs and BM-DCs. An increased IDO gene transcription level was observed in PUVA-DCs about 5 times more than in BM-DCs. The question we have to consider next is whether tolerogenic capacity is acquired only in DCs or other lymphocytes subpopulations. To test this, PUVA-treated CD4, CD8, or B220 cells from the same strain of stimulator cells were added into the MLR mixture. MLR was suppressed only when PUVA-DCs were added. Infusion of PUVA-treated DCs could have a great potential to treat lethal acute GVHD in clinical settings.
研究課題/領域番号:23791213, 研究期間(年度):2011-2012
出典：研究課題「PUVA処理制御性樹状細胞による移植片対宿主病への新たな治療戦略」課題番号23791213（KAKEN：科学研究費助成事業データベース（国立情報学研究所））（https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-23791213/23791213seika/）を加工して作成
DOI: 10.24517/00052972
Access Restrictions: 限定公開
Related Material: https://kaken.nii.ac.jp/search/?qm=10419335
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23791213/
https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-23791213/23791213seika/
Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）
https://irdb.nii.ac.jp
Original Data Provider (Database): 金沢大学 : 金沢大学学術情報リポジトリKURA