Deciphering regulatory mechanism of trained immunity in aged HSCs and clonal hematopoiesis of indeterminate potential (CHIP)

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16302
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Kobe University
• Principal Investigator: Afroj Tania 神戸大学, 医学研究科, 学術研究員 (50913034)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: Trained immunity / Humanized mouse model / Hematopoietic stem cell / aging / CHIP

Outline of Final Research Achievements

The original research proposal aimed to investigate the impact of induced trained immunity in aged HSCs and its role in CHIP pathogenesis.
To understand how human HSCs modulates the functions of its progeny populations in immune training in a relevant physiological condition, the generation of a humanized mouse model with robust engraftment of human HSCs that populated bone marrow, blood, and organs like the spleen. Xenograft tumor development in this model confirms CHIP compatibility, revealing significant human myeloid cell infiltration, key in transmitting trained immune responses from HSCs. Therefore,
the focus shifted towards elucidating the role of human myeloid cells, particularly macrophages derived from CD34+ HSCs, within this context. Current research aims to induce trained immunity in macrophages via immune modulatory treatments in aged-humanized mice, reflecting human aging. This is expected to provide deeper insights into immune training mechanisms.

Free Research Field

Immune-hematology

Academic Significance and Societal Importance of the Research Achievements

ヒト化マウスを用いた本研究により、病原体成分による老化造血幹細胞への刺激がヒト造血幹細胞自身に加えヒトマクロファージの機能にどのように影響を与えるか、訓練免疫の解明につながる成果が得られた。