Exosomal miR-216a-5p targeting TLR-4 alleviates liver ischemia-reperfusion injury by regulating M2 macrophage polarization and neutrophil inflammation.

Macrophages and neutrophil play a key role in the initiation and recovery of liver ischemia reperfusion injury (IRI) through transitions in the phenotype and induces inflammation, However, the mechanisms governing these damages have yet to be fully elucidated. Exosomes have emerged as an important mediator of cellular crosstalk in various physiological and pathological processes. This study explored the role of exosomal miRNA in macrophage polarization and liver IRI. Through high-throughput sequencing of small RNAs in exosomes, we identified the negative regulator miR-216a-5p in liver IRI. Mechanistically, miR-216a-5p skewed M2 macrophage polarization and inhibited neutrophil infiltration by targeting TLR4. In conclusion, we demonstrated that exosome-derived miR-216a-5p favors an anti-inflammatory environment by promoting the M2 polarization of macrophages and inhibiting the neutrophil inflammatory response by targeting the TLR4/NF-κB and PI3K/AKT signaling pathways, revealing the endogenous protective mechanism in liver IRI.