2023 Fiscal Year Final Research Report
Extracellular vesicles carrying self antigen impact on B cell tolerance
| Project/Area Number |
20K20465
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| Project/Area Number (Other) |
19H05555 (2019)
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| Research Category |
Grant-in-Aid for Challenging Research (Pioneering)
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| Allocation Type | Multi-year Fund (2020)
Single-year Grants (2019) |
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| Review Section |
Medium-sized Section 49:Pathology, infection/immunology, and related fields
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| Research Institution | Kansai Medical University (2023)
Institute of Physical and Chemical Research (2019-2020) |
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Principal Investigator |
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| Project Period (FY) |
2019-06-28 – 2023-03-31
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| Keywords | 細胞外微粒子 / 自己寛容 / B細胞 |
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| Outline of Final Research Achievements |
Self-reactive B cells are negatively regulated by several mechanisms, including receptor editing, cell death, and anergy, to maintain central tolerance. Engagement of an antigen and B cell receptor initiates these regulatory mechanisms. However, how can these self-antigens be delivered to the bone marrow?
Based on our study of a self-reactive antibody, BCR-expressing B cells, which are destined to be receptor-edited in vivo, bind largely to proteins related to extracellular vesicles (EVs), as shown by proteomics analysis. Administration of isolated EVs decreased the number of newly born self-reactive B cells. In contrast, administration of an EV biosynthesis inhibitor increased the number of self-reactive B cells.
Our research revealed that self-antigen-carrying extracellular vesicles in blood inhibit the emergence of self-reactive B cells. This finding provides new insight into how autoimmunity emerges and how we can prevent autoimmune diseases such as lupus.
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| Free Research Field |
免疫学
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| Academic Significance and Societal Importance of the Research Achievements |
これまでB細胞の内在的な要因、すなわちB細胞の細胞死や活性化に関わるシグナル伝達の機能不全が自己寛容の破綻に大きく関わっていると考えられていたが、本研究成果により、細胞外微粒子のデリバリーという外来性の要因が、自己免疫疾患などの発症に関わっている可能性を示し、新たな視点を提供した。今後、細胞外微粒子という新たな軸で、ヒト自己免疫疾患を見直す必要がある。今後、ヒトサンプルを用いて、本研究で確立した手法にて細胞外微粒子がヒト自己免疫疾患に影響を及ぼしているのか検討する。将来、膠原病やリュウマチなどの治療薬開発に新たなコンセプトを提供するものである。
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