2022 Fiscal Year Final Research Report
Development of the prediction marker and the preemptive therapy for chronic GVHD based on abnormal B cell homeostasis during the acute phase of allogeneic HSCT
Project/Area Number |
20K08753
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 54010:Hematology and medical oncology-related
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Research Institution | Okayama University |
Principal Investigator |
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | 血液内科学 / 造血幹細胞移植学 / 免疫寛容 / 制御性T細胞 |
Outline of Final Research Achievements |
Acute GVHD clinically develops when barrier organs such as the skin, liver, and intestinal tract are damaged above the tissue tolerance threshold by alloimmune responses with mature donor T cells. In contrast, the significance of allo-immunity to development of chronic GVHD had not been well known. In the present study, the exploratory clinical sample analyses and the validation experiments in a murine BMT model revealed that damage to primary lymphoid organs such as the bone marrow and thymus from alloimmune reactions by donor mature T cells was associated with subsequent failure of lymphogenesis of B-cell and Treg. Our results demonstrated that he functional damage of the bone marrow is the starting point of abnormal B-cell homeostasis after HSCT, and the theoretical validity of a therapeutic strategy that suppresses the onset of chronic GVHD by strategically preserving the primary lymphoid organs in acute phase.
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Free Research Field |
血液内科学、造血幹細胞移植学
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Academic Significance and Societal Importance of the Research Achievements |
慢性GVHDの病態基盤としてのB細胞恒常性異常が起こるメカニズム、またこれへの治療的介入については十分な検討がなされていなかった。今回の研究成果により、移植後超急性期の同種T細胞免疫による骨髄損傷が長期的なB細胞系列および制御性T細胞の再構築不全をきたし、慢性GVHDの発症に関与していることが明らかとなった。今回の結果を基礎として、現在、B細胞新生不全および慢性GVHD発症を予測するバイオマーカーの同定へ向けて、移植急性期における骨髄微小環境の網羅的な細胞遺伝子学的解析を進めている。一連の基礎・臨床研究は、客観的バイオマーカーに基づく慢性GVHDの評価と治療法の確立への基盤となる。
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