2022 Fiscal Year Final Research Report
Identification of potentially self-reactive T cell receptors and their candidate epitopes in a mouse model of rheumatoid arthritis
| 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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| Keywords | Autoimmunity / T cell receptor / single cell sequencing |
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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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| Free Research Field |
Autoimmune disease
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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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