| Project/Area Number |
22K15448
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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 49040:Parasitology-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2022-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2022: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | Malaria / Bone marrow / Hematopoiesis / B cells / lymphopoiesis / hematopoiesis / bone marrow niche / B cell / bone marrow / hematopoietic niche / malaria / Infection |
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| Outline of Research at the Start |
We previously found that malaria causes bone loss and alters bone marrow hematopoiesis. We recently found changes in bone marrow niches that governs hematopoiesis. This proposal aims to elucidate the molecular mechanisms that contribute to the alteration of bone marrow niches during malaria infection.
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| Outline of Final Research Achievements |
Infection and inflammation may contribute to the damage of bone marrow hematopoietic stem cell (HSC) niches. In this study, we found that malaria suppresses B lymphocytic niche in the bone marrow through the alteration of CXCL12-abundant reticular (CAR) cells. Despite the decreased of CAR cell population, malaria enhances the expansion of hematopoietic stem and progenitor cells (HSPCs). However, the differentiation potential of HSPCs is imbalance during malaria. The suppression of both CAR cells and osteoblasts dampens B lymphopoiesis and the maintenance of B cells in the bone marrow. The decreased of pre-existing long-lived plasma cells in the bone marrow during malaria infection may contribute to compromised humoral immunity(Lee MSJ et al., 2024, International Immunology).
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| Academic Significance and Societal Importance of the Research Achievements |
This study reveals the effect of malaria on immune cell development in the bone marrow. We found that malaria reduced pre-existing long-lived plasma cells in the bone marrow, which raises the concern of impaired antibody responses against other infections after malaria infection.
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