| Project/Area Number |
20K16286
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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 49070:Immunology-related
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| Research Institution | National Institutes of Biomedical Innovation, Health and Nutrition (2021-2022)
Osaka University (2020) |
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Principal Investigator |
LLAMAS COVARRUBIAS Mara Anais 国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 ワクチン・アジュバント研究センター, 研究員 (00867715)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2021: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2020: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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| Keywords | Autoimmunity / T cell receptor / single cell sequencing / Rheumatoid arthritis / T Cell Receptor / Rheumatoid Arthritis / epitope |
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| Outline of Research at the Start |
The activating peptides and the receptor molecules responsible for the development of autoimmune diseases are largely unknown. We aim to identify candidate self-reactive receptor-peptide pairs in a mouse model of Rheumatoid Arthritis, by single cell sequencing and machine learning.
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| Outline of Final Research Achievements |
Autoimmune diseases such as rheumatoid arthritis (RA) are an important cause of morbidity and disability worldwide. In spite of intensive study, the T cell receptor (TCR) molecules responsible for autoimmune disease are largely unknown. By studying mice with impaired TCR signaling, it has been hypothesized that a shift in the TCRs from regulatory (Treg) to conventional (Tconv) cells plays a role in self-reactivity. Here, by using single cell sequencing, we identified several groups of autoreactive T cells and their TCRs in joints, lymph nodes and spleen of a mouse model of RA. We found three groups of self-reactive cells according to their gene programs, where two of them are also highly similar in their TCRs. The other group is unique in terms of both gene program and TCRs, and only occurs in joints. Moreover, we compared the similitude between self-reactive Tconv TCRs and normal Treg and Tconv TCRs and our results provide support for the hypothesis of the repertoire shift.
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| Academic Significance and Societal Importance of the Research Achievements |
We provided a novel description of the gene programs and TCRs involved in autoimmunity and showed evidence of a Treg/Tconv repertoire shift. These results, increase our current understanding of the pathogenesis of autoimmune diseases and generate new hypothesis that can be tested in future research.
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