2022 Fiscal Year Final Research Report
Elucidation of the fundamental mechanism underlying hematopoietic control changes through a novel immune evasion mechanism in autoimmune bone marrow failure
| Project/Area Number |
20K08707
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 54010:Hematology and medical oncology-related
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
細川 晃平 金沢大学, 附属病院, 助教 (10786239)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | iPS細胞 / HLA / 自己免疫疾患 / 造血幹細胞 / 骨髄移植 / 免疫不全マウス |
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| Outline of Final Research Achievements |
Aplastic anemia is a disorder that results in hematopoietic failure due to T cells attacking hematopoietic progenitor cells (HSPCs). However, the mechanisms that regulate hematopoietic control and immune evasion in HSPCs are not yet fully understood. This study aimed to investigate the expression of CXCR4, a chemokine involved in hematopoietic control, in HSPCs with diverse phenotypes. The results suggest that diverse immune evasion mechanisms and changes in hematopoietic control are required for steady hematopoiesis among HSPCs. Transplantation experiments using HSPCs induced from patient iPS cells revealed that CXCR4 expression may be controlled as epigenetic memory, which explains the observed changes in hematopoietic control in autoimmune aplastic anemia. These findings provide insights into hematopoietic control and CXCR4 expression in HSPCs, as well as potential novel therapies for hematopoietic failure.
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| Free Research Field |
免疫学
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| Academic Significance and Societal Importance of the Research Achievements |
自己免疫性骨髄不全は、造血幹前駆細胞に対する自己の細胞傷害性T細胞の攻撃が発端となり発症する造血不全である。本研究において、患者iPS細胞から誘導した造血幹前駆細胞を用いた実験により、造血制御関連ケモカインであるCXCR4の発現が多様な表現型を有する造血幹前駆細胞の間で乖離しているとともに、その発現がepigenetic memoryとして制御されている可能性を示した。本研究成果は、造血制御機構の解明に大きく貢献するとともに、骨髄不全患者の良性および前がん性クローン性造血の鑑別に役立つ可能性が考えられる。また、将来的には個別化医療の進展にも繋がることが期待される。
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