制御性樹状細胞の大量培養を用いた新たな造血幹細胞移植の開発

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: 2011-05-18

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Note (General)：: マウス骨髄細胞からGM-CSFを添加し未熟樹状細胞を大量に培養した後、psolarenと紫外線を併用し(いわゆるPUVA療法の応用)制御性樹状細胞を大量に作製することに成功した。その細胞は、混合リンパ球反応(MLR)においてMHC非拘束性に抑制性の機能を有していた。メカニズムは、抗炎症性サイトカイン...

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

https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21790973/

https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-21790973/21790973seika/

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Material Type: 文書・図像類
Title: 制御性樹状細胞の大量培養を用いた新たな造血幹細胞移植の開発
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: 2011-05-18
Publication Date (W3CDTF): 2011-05-18
Alternative Title: The treatment strategy for GVHD by infusion of PUVA-treated dendritic cells
Periodical title: 平成22(2010)年度科学研究費補助金若手研究(B) 研究成果報告書 = 2010 Fiscal Year Final Research Report
No. or year of volume/issue: 2009-2010
Volume: 2009-2010
Pages: 6p.-
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): マウス骨髄細胞からGM-CSFを添加し未熟樹状細胞を大量に培養した後、psolarenと紫外線を併用し(いわゆるPUVA療法の応用)制御性樹状細胞を大量に作製することに成功した。その細胞は、混合リンパ球反応(MLR)においてMHC非拘束性に抑制性の機能を有していた。メカニズムは、抗炎症性サイトカイン(IL-10やTGF-β)によるものではなく、細胞間の接触によって引き起こされていた。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、骨髄由来の樹状細胞に比べて5倍以上発現していた。IDOを発現し、MHC非拘束性に抑制機能を有するPUVA処理した樹状細胞による細胞療法は、致死的なGVHDに対して有用な治療法と成りうる可能性がある。
Bone marrow-derived cultured DCs acquired tolerogenicity by PUVA (psoralen+UVA) treatment in mice. In MLR assays, strong tolerogenicity was observed when adding PUVA-DCs generated from the same strain of stimulator cells, or responder cells, or even from third party strain into MLR mixture. That is, the PUVA-treated DCs have tolerogenic function in a MHC-independent manner, in part, due to the reduced expression levels of CD80 and CD86. To clarify the mechanisms of how PUVA-treated DCs induce tolerogenicity in further detail, we performed MLR with the addition of neutralizing antibodies against IL-10 or TGF-b1 or both. Neutralization of immunosuppressive cytokines had no effects on MLR. We then showed that cell-to-cell contact between PUVA-DCs and alloreactive T-cells was needed to mediate the regulatory effect by transwell experiment. Next 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 increase IDO gene transcription level was observed in PUVA-DCs about 5 times more than in BM-DCs (p<0.01). In conclusion, PUVA-DCs acquired regulatory function in a MHC-independent manner by upregulation of IDO. Infusion of PUVA-treated DCs could have a great potential to treat lethal acute GVHD in clinical settings.
出典：研究課題「制御性樹状細胞の大量培養を用いた新たな造血幹細胞移植の開発」課題番号21790973（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-21790973/21790973seika/）を加工して作成
DOI: 10.24517/00052973
Access Restrictions: 限定公開
Related Material: https://kaken.nii.ac.jp/search/?qm=10419335
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21790973/
https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-21790973/21790973seika/
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