Splenic CD169 + Tim4 + Marginal Metallophilic Macrophages Are Essential for Wound Healing After Myocardial Infarction
Authors' conclusion
Splenic CD169+Tim4+ MMMs are required for proresolving and reparative responses after MI and can be manipulated for therapeutic benefit to limit long-term heart failure.
Study context
- Population
- Mice with surgical myocardial infarction (MI); humans with STEMI and controls with stable CAD undergoing elective PCI
Methodological detailsmurine models, human flow cytometry substudy
- Murine models
- Human flow cytometry substudy
Main finding
As reported in the abstract
- Splenic CD169+Tim4+ marginal metallophilic macrophages (MMMs) circulate in blood as Ly6Clow monocytes expressing macrophage markers and help populate CD169+Tim4+CCR2-LYVE1low macrophages in the naive heart
- After acute MI, splenic MMMs augment phagocytosis and CCR3/CCR4 expression and robustly mobilize to the heart, markedly expanding cardiac CD169+Tim4+LYVE1low macrophages with an immunomodulatory, proresolving gene signature
- These macrophages are obligatory for apoptotic neutrophil clearance, suppression of inflammation and induction of a reparative macrophage phenotype in the infarcted heart
- Splenic MMMs are necessary and sufficient for post-MI wound healing and limit late pathological remodeling
- Liver X receptor-α agonist-induced expansion of splenic marginal zone and MMMs during acute MI alleviates inflammation and improves short- and long-term cardiac remodeling
- Humans with acute STEMI show expansion of circulating CD169+Tim4+ cells, primarily within intermediate (CD14+CD16+) monocytes
Original publication
Splenic CD169 + Tim4 + Marginal Metallophilic Macrophages Are Essential for Wound Healing After Myocardial Infarction. Circulation. Published 28 April 2025. doi:10.
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