YAP-Dependent Induction of CD47-Enriched Extracellular Vesicles Inhibits Dendritic Cell Activation and Ameliorates Hepatic Ischemia-Reperfusion Injury

Figure 7

Mechanism diagram for the immunosuppression effect of YAP/F-actin/EV-CD47 axis on DCs in hepatic IRI. IR stress stimulated YAP expression in normal hepatocytes and promoted the remodeling of F-actin to form an endosomal trafficking network, which is critical for EV formation. These EVs were rich in CD47, which could bind to CD172a receptor on DCs. In normal conditions, most of the MVB would form into EVs with a little few into lysosome. When YAP expression was knocked down, however, F-actin failed to gather around and form a network report; thus, the amount of EVs decreased with more vesicles engulfed by lysosome. The amount of CD47 was scarce, and CD172⁺ DCs were activated and led to more severe damage. Therefore, EVs lack of CD47⁺ due to YAP knockout in hepatocytes, activated DCs, and aggregated hepatic IRI, while YAP activation induced by hepatic IRI promoted the secretion of CD47-enriched EVs by remodeling of cytoskeleton F-actin, and CD47⁺ EVs induced the immunosuppressive DCs and protected the liver from IRI. CD47⁺ EV supplement could be a novel therapeutic strategy for hepatic IRI treatment.