J Immunol. 2026 Aug 4;215(8):vkag226. doi: 10.1093/jimmun/vkag226.
ABSTRACT
CCR2+ monocytes are recruited to sites of acute myocardial injury, where they play a critical role in clearing necrotic debris and replenishing the depleted resident macrophage population. Although this response is necessary for early tissue repair, prolonged activation of inflammatory pathways and persistent recruitment of CCR2+ monocytes have been associated with accelerated ventricular remodeling and adverse outcomes. Inhibition of CCR2 has shown promise in preclinical models of myocardial injury and represents a potential therapeutic target. Cardiosphere-derived cell extracellular vesicles (CDC-EVs) have demonstrated cardioprotective effects partly through modulation of the immune response. We investigated whether CDC-EVs regulate inflammatory monocyte trafficking through effects on CCR2 signaling. We found that CDC-EVs reduce the surface availability of CCR2 on human monocytes through an miR-146a-dependent mechanism, resulting in decreased monocyte migration toward CCL2. These findings identify a previously unrecognized mechanism by which CDC-EVs modulate CCR2-dependent monocyte trafficking and provide new insight into how EVs regulate innate immune responses after myocardial injury.
PMID:42568044 | DOI:10.1093/jimmun/vkag226