Regulatory T cells and their Potential for Tolerance Induction in Myasthenia Gravis Towards Precision Medicine
Project/Area Number |
19K07206
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 47060:Clinical pharmacy-related
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Research Institution | Tokyo University of Pharmacy and Life Science |
Principal Investigator |
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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Keywords | 重症筋無力症 / 制御性T細胞 / エピジェネティック制御 / プレシジョンメディスン / 重症筋無力症患者 |
Outline of Research at the Start |
MGでは眼瞼下垂,複視などの眼症状,四肢・頸筋の筋力低下,構音障害,嚥下障害が認められ,重症例では呼吸障害を来す.本研究では,このようなMG症状を軽減あるいは消失させる治療法や再発予防策を確立する.申請者らは,MG患者末梢におけるTreg細胞数が低下していることをすでに明らかとしている.そこで,MG患者におけるTreg細胞の分化あるいは抑制機能を制御する遺伝子に着目し,自己免疫寛容の誘導を目的とした治療の有用性について明らかとする.MG患者PBMCを用いて,Treg細胞に関連するゲノム情報あるいは分子情報を解析する.過剰な自己免疫応答を制御するために有効な治療法を探索する.
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Outline of Final Research Achievements |
The transcription factor forkhead box P3 (FOXP3) is specifically expressed in CD4+CD25+ regulatory T (Treg) cells, and it is regarded as a critical developmental and functional factor for Treg cells. We found that the FOXP3 gene methylation in patients with myasthenia gravis was significantly higher than healthy subjects, which could contribute the immunodeficiency of MG. However, it was not shown that the influence of the enzyme for demethylation, TET2 on the stable FOXP3 expression. Interleukin-10 (IL-10) is a pleiotropic cytokine with an important anti-inflammatory and contributed to the immunoregulatory function of Treg cells. In this study, we showed the relationship between the percentage of IL-10+CD19+ B cells and the frequency of Treg cells in CD4+ T cells. We also demonstrated that the IL-10 production on CD4+ T cells was elevated in the MG patients with the galactose-deficient IgG.
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Academic Significance and Societal Importance of the Research Achievements |
本研究によりMG患者Treg細胞の分化誘導にFOXP3遺伝子のメチル化制御が有用である可能性が示唆された.抗炎症性サイトカインであるIL-10がTreg細胞の誘導に関与するとともに,MG患者由来IgGにおけるガラクトース欠損のレベルとの関連が明らかとなった.自己免疫疾患における分子標的薬による治療戦略の構築に,末梢血免疫細胞のタイピングに基づくプレシジョンメディスンの可能性を示したものと思われる.
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Report
(4 results)
Research Products
(6 results)
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[Journal Article] Tetrandrine and cepharanthine induce apoptosis through caspase cascade regulation, cell cycle arrest, MAPK activation and PI3K/Akt/mTOR signal modification in glucocorticoid resistant human leukemia Jurkat T cells2019
Author(s)
Wencheng Xu W, Xiaoqin Wang, Yuanchao Tu, Hiroshi Masaki, Sachiko Tanaka, Kenji Onda, Kentaro Sugiyama, Haruki Yamada, Toshihiko Hirano
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Journal Title
Chem Biol Interact
Volume: 310
Pages: 108726-108726
Related Report
Peer Reviewed
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