| Project/Area Number |
16K08740
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Yamaguchi University (2018)
Kyushu University (2016-2017) |
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Principal Investigator |
SHIBATA Kensuke 山口大学, 大学院医学系研究科, 講師 (50529972)
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| Research Collaborator |
YAMASAKI Sho
OGAWA Yoshihiro
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | 自己免疫疾患 / 代謝産物 / T細胞 / 自己抗体 / 疾患モデル動物 / 自己免疫性疾患 |
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| Outline of Final Research Achievements |
Autoimmune diseases are frequently caused by pathogenic T cells, but identities of the pathogenic T cell subsets remain unclear. Here we established a mouse model in which spontaneously develops a fatal autoimmune disease with severe pancreatic inflammation accompanied by autoantibody deposition and B cell infiltration. We found that MR1-restricted αβ T (MR1T) cells expanded in response to pancreas-derived autoantigens and genetic deletion of MR1T cells significantly prolonged their survival. The disease manifestations in mice recapitulated human autoimmune pancreatitis (AIP) and, frequency of activated MR1T cells was significantly enhanced in AIP patients. Thus, our study provides a novel insight into the mechanism of T cell-mediated autoimmune diseases.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、我々が独自に樹立したヒトIgG4関連疾患様病態自然発症マウスモデルを用いた臨床応用研究であり、極めて独創性が高く学術的意義は高い。また、ヒトIgG4関連疾患の病態を反映したバイオマーカーは未だ同定されておらず、今後の研究で我々が同定した病原性MR1T細胞のバイオマーカーとしての有効性が示されれば、世界初のIgG4関連疾患発症や再発を予測できる手法となることが期待され社会的ニーズも高いと考えられる。
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