Immune–fibroblast ligand–receptor axes in post-infarction cardiac remodeling: convergent and divergent mechanisms compared with cancer-associated fibroblasts
- 1The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)
- 2Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Zhengzhou University
- 3Department of Urology, The Second Affiliated Hospital of Zhejiang University
Abstract
Myocardial infarction-triggered cardiac fibrosis is a cardinal feature of maladaptive ventricular remodeling and a principal contributor to heart failure pathogenesis. Enabled by single-cell RNA sequencing and spatial transcriptomics, accumulating evidence demonstrates that post-infarction fibrosis represents an actively coordinated biological program rather than a passive wound-healing event, which is governed by ligand-receptor-mediated crosstalk between immune cells and cardiac fibroblasts. Pioneering work has established monocyte-derived macrophages as a predominant cellular source of pro-inflammatory interleukin-1β; upon binding its cognate receptor on fibroblasts, this cytokine instigates the generation of pro-fibrotic fibroblast subsets within spatially segregated niches of the infarcted myocardium. Multiple additional ligand-receptor modules, encompassing osteopontin-CD44/integrin, transforming growth factor-β, platelet-derived growth factor, as well as growth arrest-specific protein 6-MER tyrosine kinase, further fine-tune fibroblast activation trajectories in a spatiotemporally-restricted fashion. Intriguingly, a substantial fraction of these ligand-receptor interactions are conserved in cancer-associated fibroblast biology, wherein osteopontin-producing macrophages and activated fibroblasts collaboratively build pro-tumor stromal microenvironments. We consolidate recent multi-omic findings regarding immune-fibroblast ligand-receptor communication during post-infarction cardiac remodeling, highlight mechanistic analogies to cancer-associated fibroblast activation, and discuss therapeutic prospects arising from targeting these conserved signaling nodes across cardiac and neoplastic diseases.
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BibTeX
@article{lu2026immunefibroblast,
title = {{Immune–fibroblast ligand–receptor axes in post-infarction cardiac remodeling: convergent and divergent mechanisms compared with cancer-associated fibroblasts}},
author = {Hong Lu and Xiao-long Tao and Ding-ming Song and Yi-bo He and Lan-zhi Zheng},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1992368},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1992368/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Immune–fibroblast ligand–receptor axes in post-infarction cardiac remodeling: convergent and divergent mechanisms compared with cancer-associated fibroblasts
AU - Hong Lu
AU - Xiao-long Tao
AU - Ding-ming Song
AU - Yi-bo He
AU - Lan-zhi Zheng
PY - 2026
DA - 2026/10/28
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1992368
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1992368/full
AB - Myocardial infarction-triggered cardiac fibrosis is a cardinal feature of maladaptive ventricular remodeling and a principal contributor to heart failure pathogenesis. Enabled by single-cell RNA sequencing and spatial transcriptomics, accumulating evidence demonstrates that post-infarction fibrosis represents an actively coordinated biological program rather than a passive wound-healing event, which is governed by ligand-receptor-mediated crosstalk between immune cells and cardiac fibroblasts. Pioneering work has established monocyte-derived macrophages as a predominant cellular source of pro-inflammatory interleukin-1β; upon binding its cognate receptor on fibroblasts, this cytokine instigates the generation of pro-fibrotic fibroblast subsets within spatially segregated niches of the infarcted myocardium. Multiple additional ligand-receptor modules, encompassing osteopontin-CD44/integrin, transforming growth factor-β, platelet-derived growth factor, as well as growth arrest-specific protein 6-MER tyrosine kinase, further fine-tune fibroblast activation trajectories in a spatiotemporally-restricted fashion. Intriguingly, a substantial fraction of these ligand-receptor interactions are conserved in cancer-associated fibroblast biology, wherein osteopontin-producing macrophages and activated fibroblasts collaboratively build pro-tumor stromal microenvironments. We consolidate recent multi-omic findings regarding immune-fibroblast ligand-receptor communication during post-infarction cardiac remodeling, highlight mechanistic analogies to cancer-associated fibroblast activation, and discuss therapeutic prospects arising from targeting these conserved signaling nodes across cardiac and neoplastic diseases.
SN - 1664-3224
ER -