Induction of the responsible antigen-specific regulatory T cells in type 1 diabetes
| Project/Area Number |
17K09854
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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 |
Metabolomics
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| Research Institution | University of Toyama (2019)
National Center for Global Health and Medicine (2017-2018) |
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Principal Investigator |
Chujo Daisuke 富山大学, 学術研究部医学系, 特命教授 (30640528)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 1型糖尿病 / 自己免疫 / T細胞 |
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| Outline of Final Research Achievements |
The aim of this study is to identify islet antigen-specific T cell responses in the three subtypes of type 1 diabetes (T1D); acute onset (AT1D), slowly progressive (SP1D), and fulminant T1D (FT1D); and to induce the responsible antigen-specific regulatory T cells. We found that islet antigen-specific Th1 responses were up-regulated in AT1D and FT1D, and the specific Tr1 cell responses were diminished in FT1D. Furthermore, FT1D displayed the highest frequencies of islet antigen-specific CD8 T cells among the three subtypes of T1D. We are currently trying the induction of the antigen-specific regulatory T cells by using autologous dendritic cells that were differentiated from monocyte by using cytokines and educated with the responsible antigen peptides.
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| Academic Significance and Societal Importance of the Research Achievements |
1型糖尿病は自己免疫による膵島細胞（インスリン分泌細胞）の破壊よって発症する疾患であるが、原因不明な点が多い。本研究では、1型糖尿病の各タイプ（急性発症型、緩徐進行型、劇症型）では自己免疫反応が異なり、急性発症型や劇症型では膵島細胞の破壊に関与する病原性の免疫反応が強いことを発見した。また劇症型では自己免疫を制御するブレーキの働きが弱っていることも判明した。この研究データをもとに1型糖尿病の発症に関わる自己免疫反応を抑えることが可能かどうかについて患者の血液を用いて研究を続けており、これが達成されれば自己免疫による膵島細胞の破壊を防ぐような新しい治療法の開発につながる可能性がある。
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Report
(4 results)
Research Products
(6 results)
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[Presentation] Distinct Islet Antigen-Specific CD8+ T Cell Responses among the Three Subtypes of Type 1 Diabetes2019
Author(s)
Daisuke Chujo, Maya Matsushita, Akitsu Kawabe, Chiharu Tsutsumi, Fumitaka Haseda, Akihisa Imagawa, Toshiaki Hanafusa, Masayuki Shimoda, Kohjiro Ueki, Hiroshi Kajio, Kunimasa Yagi, Kazuyuki Tobe
Organizer
55th Annual Meeting of the European Association for the Study of Diabetes
Related Report
Int'l Joint Research
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[Presentation] Distinct Phenotypes of Islet Antigen-Specific CD4+ T Cells among the Three Subtypes of Type 1 Diabetes2018
Author(s)
Daisuke Chujo, Akitsu Kawabe, Nobuyuki Takahashi, Maya Matsushita, Chiharu Tsutsumi, Fumitaka Haseda, Akihisa Imagawa, Toshiaki Hanafusa, Kunimasa Yagi, Masayuki Shimoda, Kohjiro Ueki, Hiroshi Kajio
Organizer
78th American Diabetes Association Scientific Sessions
Related Report
Int'l Joint Research
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[Presentation] Distinct Phenotypes of Islet Antigen-Specific CD4+ T Cells among the Three Subtypes of Type 1 Diabetes2018
Author(s)
Daisuke Chujo, Akitsu Kawabe, Nobuyuki Takahashi, Maya Matsushita, Chiharu Tsutsumi, Fumitaka Haseda, Akihisa Imagawa, Toshiaki Hanafusa, Kunimasa Yagi, Masayuki Shimoda, Kohjiro Ueki, Hiroshi Kajio
Organizer
The 78th American Diabetes Association Scientific Sessions
Related Report
Int'l Joint Research
