PUVA処理した制御性樹状細胞によるヒトGVHDに対する新たな細胞療法の開発

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Author: 前馬, 秀昭ほか

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Publication date: 2017-05-24

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Note (General)：: 金沢大学附属病院小児科マウス骨髄細胞からpsolaren と紫外線(UVA)を用いて、制御性樹状細胞(PUVA-DC)を作製する技術を開発した。In vitroの解析ではMHC 非依存性にT リンパ球に対し抑制作用を示し、細胞間接着およびIDO増加による免疫寛容誘導が示唆された。しかしIDO阻害物質...

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Material Type: 文書・図像類
Title: PUVA処理した制御性樹状細胞によるヒトGVHDに対する新たな細胞療法の開発
Author/Editor: 前馬, 秀昭
Maeba, Hideaki
Author Heading: 前馬, 秀昭
Maeba, Hideaki
Publication Date: 2017-05-24
Publication Date (W3CDTF): 2017-05-24
Alternative Title: Development of the new cell therapy for GVHD using tolerogenic dendtiric cells treated by PUVA treatment
Periodical title: 平成28(2016)年度科学研究費補助金基盤研究(C) 研究成果報告書 = 2016 Fiscal Year Final Research Report
No. or year of volume/issue: 2014-04-01 - 2017-03-31
Volume: 2014-04-01 - 2017-03-31
Pages: 4p.-
Text Language Code: jpn
Subject Heading: 制御性樹状細胞
PUVA
GVHD
Target Audience: 一般
Note (General): 金沢大学附属病院小児科
マウス骨髄細胞からpsolaren と紫外線(UVA)を用いて、制御性樹状細胞(PUVA-DC)を作製する技術を開発した。In vitroの解析ではMHC 非依存性にT リンパ球に対し抑制作用を示し、細胞間接着およびIDO増加による免疫寛容誘導が示唆された。しかしIDO阻害物質下におけるリンパ球混合培養では免疫抑制作用は解除されなかった。マウスGVHDモデルでPUVA-DC（Host,Donor,Third-party）を輸注したがGVHD抑制作用は認めなかった。生体内での生着・生存が不十分であることが考えられ、生体内投与後においても生存するPUVA-DC作成を探索する研究へと繋がった。
Bone marrow-derived cultured DCs acquired tolerogenicity by PUVA (psoralen+UVA) treatment in mice. In vitro assays, strong tolerogenicity was observed when adding PUVA-DC even from third party strain into MLR. That is, the PUVA-DC have tolerogenic function in a MHC-independent manner. We showed that cell-to-cell contact was needed to mediate the regulatory effect by transwell experiment. Next, we compared the expression of the IDO, which induces T-cell anergy, by real-time PCR between PUVA-DC and BM-DC. An increase IDO gene transcription level was observed in PUVA-DC about 5 times more than in BM-DC. But adding 1-MT, which is an inhibitor of IDO, had no effects on MLR with PUVA-DC.We transfused PUVA-DC (Host-type, Donor-type, Third-party-type) in a mouse GVHD model, but the GVHD inhibitory effects were not observed. It was thought the survival of PUVA-DC was insufficient. These data leads us to search for technique to make PUVA-DC to survive after in vivo administration.
研究課題/領域番号:26461604, 研究期間(年度):2016-04-01 - 2018-03-31
DOI: 10.24517/00052971
Access Restrictions: 限定公開
Related Material: https://kaken.nii.ac.jp/search/?qm=10419335
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-26461604/
https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-26461604/26461604seika/
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