Altered bone marrow niche forms central innate immune memory driving cardiac dysfunction

We previously showed that heart failure induces innate immune memory in hematopoietic stem and progenitor cells, which contributes to recurrence of heart failure and impaired stress responses in multiple organs. While the bone marrow microenvironment maintains blood cell formation, its role in this memory remains poorly understood. Here we show that bone marrow mesenchymal stromal cells expressing the leptin receptor influence hematopoietic stem and progenitor cells to promote cardiac pathology. Transplanting these stromal cells from mice with heart failure together with healthy hematopoietic cells caused inflammatory macrophages to accumulate in the heart and worsened cardiac remodeling. Mechanistically, heart failure reduced a stromal subpopulation producing heparin-binding epidermal growth factor and suppressed growth factor signaling in hematopoietic cells. Heart failure also activated a fat-forming program in stromal cells. Notably, an equivalent stromal subpopulation exists in human bone marrow, and heart failure was associated with increased bone marrow fat in humans, identifying the bone marrow microenvironment as a regulator of innate immune memory.

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Publication Details

Journal
Nature Communications
Published
2026-08-26
DOI
https://doi.org/10.1038/s41467-026-76178-z
Primary Topic
Cardiac Fibrosis and Remodeling
Type
article
Field-Weighted Citation Impact
0.00

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article

Altered bone marrow niche forms central innate immune memory driving cardiac dysfunction

Kohsaku Goto, Katsuhito Fujiu, Eriko Hasumi, Yiyi Yang et al.
Nature Communications
Cardiac Fibrosis and Remodeling
article

Altered bone marrow niche forms central innate immune memory driving cardiac dysfunction

Kohsaku Goto, Katsuhito Fujiu, Eriko Hasumi, Yiyi Yang, Tsukasa Oshima, Atsushi Kobayashi, Ichiro Manabe, Junichi Sugita, Yukiteru Nakayama, Ryoko Uchida, Naoto Setoguchi, Issei Komuro, Jiaxin Ku, Takashi Nagasawa, Yuxiang Liu, Kunihito Kani, Norihiko Takeda
article en

Abstract

We previously showed that heart failure induces innate immune memory in hematopoietic stem and progenitor cells, which contributes to recurrence of heart failure and impaired stress responses in multiple organs. While the bone marrow microenvironment maintains blood cell formation, its role in this memory remains poorly understood. Here we show that bone marrow mesenchymal stromal cells expressing the leptin receptor influence hematopoietic stem and progenitor cells to promote cardiac pathology. Transplanting these stromal cells from mice with heart failure together with healthy hematopoietic cells caused inflammatory macrophages to accumulate in the heart and worsened cardiac remodeling. Mechanistically, heart failure reduced a stromal subpopulation producing heparin-binding epidermal growth factor and suppressed growth factor signaling in hematopoietic cells. Heart failure also activated a fat-forming program in stromal cells. Notably, an equivalent stromal subpopulation exists in human bone marrow, and heart failure was associated with increased bone marrow fat in humans, identifying the bone marrow microenvironment as a regulator of innate immune memory.

Nature CommunicationsVol. 17(1)
Chiba University (JP), Tokyo Fuji University (JP), Tohoku University (JP), Tokyo Metropolitan Institute of Medical Science (JP), Integrative Medicine Institute (US), The University of Tokyo (JP), International University of Health and Welfare (JP), The University of Osaka (JP)
Japan Foundation for Applied Enzymology, Secom Science and Technology Foundation, Japan Society for the Promotion of Science, Japan Science and Technology Agency
Good health and well-being
Openalex Percentile: Top 11%
Cardiac Fibrosis and Remodeling
DOIOpen Access PDFOpenAlex
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