2022 Fiscal Year Annual 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 Institution | National Institutes of Biomedical Innovation, Health and Nutrition |
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Principal Investigator |
LlamasCovarrubias MaraAnais 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 / Rheumatoid arthritis |
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| Outline of Annual Research Achievements |
In order to study self-reactive T cell receptor (TCR) and their likely target antigens we performed single cell repertoire and gene expression analysis on regulatory (Treg) and conventional (Tconv) cells from mice with impaired TCR signaling (ZAC) and WT mice. Our initial analysis allowed to identify Th17 cells in ZAC mice tissues, but we could not completely remove a batch effect with the current techniques, so we decided to improve the analysis by treating each tissue separately. This led us to identify three different subgroups of Th17 cells in arthritic Joints and their possible differentiation trajectories. We discovered that the most differentiated Th17 cells have unique repertoires with a very low degree of sharing with other Th17 cells in joints or in other tissues. In addition, we have identified a set of potential gene candidates involved in the specific differentiation of Th17 cells within the inflamed joint. We propose a multistep model for T cell effector specialization and tissue adaptation influenced by the repertoire and possibly by local antigen presentation from tissue resident macrophages. A paper has been published and a second paper is being prepared. An abstract has been submitted for the International Congress of Immunology (IUIS) 2023.
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