| Project/Area Number |
21K20933
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0904:Internal medicine of the bio-information integration and related fields
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| Research Institution | Kyoto University (2022)
Kobe University (2021) |
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Principal Investigator |
KANIE Keitaro 京都大学, iPS細胞研究所, 研究員 (90905829)
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| Project Period (FY) |
2021-08-30 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | iPS細胞 / 下垂体機能低下症 / 自己免疫疾患 / 自己免疫性下垂体疾患 / 自己免疫性下垂体炎 / キラーT細胞 / 細胞傷害性T細胞 / 抗原特異的キラーT細胞 / 抗原特異的CTL / 抗PIT-1下垂体炎 / in vitro疾患モデル / 自己反応性T細胞 |
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| Outline of Research at the Start |
自己免疫性下垂体疾患は、医療費助成対象の指定難病であり自己免疫機序が推定されているがその本態は明らかではない。本研究では、自己免疫性下垂体疾患の一つである自己免疫性下垂体炎の患者由来iPS細胞を利用した疾患モデルを作成し、細胞性免疫あるいは液性免疫の細胞傷害への関与を明らかにし、その発症メカニズムを解明する。
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| Outline of Final Research Achievements |
Few models using induced pluripotent stem cells (iPSCs) have been reported for autoimmune diseases. Anti-pituitary-specific transcription factor (PIT)-1 hypophysitis is caused by autoimmunity against PIT-1-expressing anterior pituitary cells, and cytotoxic T cells (CTLs) play an essential role in the disease. Using tissues expressing the same human leukocyte antigen (HLA) is essential for establishing a T cell-mediated autoimmune disease model; therefore, we used patient-derived iPSCs. First, we cloned PIT-1-specific CTLs and determined the set of epitopes and T cell receptors. Then we analyzed the cytotoxicity of the iPSC-derived pituitary cells in co-culture with CTLs. Activation of CTLs and PIT-1-positive cell-specific cytotoxicity were observed only in co-culture of iPSC-derived pituitary cells and PIT-1-specific CTLs. Furthermore, we determined specific T cell receptors and HLA haplotypes. Specific cytotoxicity was inhibited by immunosuppressive agents.
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| Academic Significance and Societal Importance of the Research Achievements |
一部の自己免疫疾患では、その発症に特異的なキラーT細胞の関与が示唆されているが、特異的抗原の同定および病原性キラーT細胞の単離は困難であった。本研究では、①患者末梢血液より病原性をもつキラーT細胞を単離する方法を開発し、②自己免疫性下垂体炎の患者由来iPS細胞を利用した疾患モデルを作成した。
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