| Project/Area Number |
18K16141
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 54020:Connective tissue disease and allergy-related
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
Hasegawa Hisanori 東京医科歯科大学, 東京医科歯科大学病院, 講師 (00707028)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | ヒトiPS細胞由来筋細胞 / 筋細胞傷害 / 多発性筋炎 / 筋細胞-CD8T細胞共培養 / 筋細胞-CD8T細胞共培養系 / 筋細胞-CD8T細胞-マクロファージ混合培養 / 筋細胞-CD8T細胞-マクロファージ共培養 |
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| Outline of Final Research Achievements |
Polymyositis and dermatomyositis (PM/DM) are systemic autoimmune diseases. Conventional immunosuppressants used to treat PM/DM are non-specific to the pathological conditions of PM/DM. Hence there are many cases refractory to those immunosuppressants. Novel treatments specific to the pathological conditions of PM/DM are required. We have elucidated that both autoaggressive cytotoxic CD8 T cells (CTL) and the activation of local innate immunity in the muscles are necessary for the development of autoimmune myositis. Although we observe macrophages (Mφ) in the muscle lesions of PM/DM patients, it is not fully understood how Ｍφ activate the local innate immunity.
To evaluate how Mφ modulate the cytotoxicity of CTL in a human muscle cell-CTL-Mφ mixed culture, which is an ex vivo model of the muscle lesions of PM/DM patients, we initially developed a cytotoxic assay with human iPS cells (hiPSC) derived CTL attacking muscle cells differentiated from hiPSC antigen specifically.
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| Academic Significance and Societal Importance of the Research Achievements |
日本でPM患者の疾患特異的hiPSCを用いてPM/DMの研究を行っているのは当研究室のみであり、また、hiPSCから分化させたヒト筋細胞に対する抗原特異的なヒトCTLによる細胞傷害系の確立と、その培養系にMφを加えて、MφのPM/DMの病態への関与や自然免疫活性化機序の解明を目的とする本研究は非常に独時性が高い研究と考える。また本研究は、PM/DMの病態に基づいた治療標的を提唱し、PM/DMの革新的な治療法の開発につながるだけでなく、政府が健康医療戦略2015で提唱した、疾患特異的hiPSCを用いた難病・希少疾病等の原因解析や創薬等に係る研究である点も非常に意義の高い研究である。
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