Annexin A1 mRNA-loaded liposomes alleviate acute pancreatitis by suppressing STING pathway and promoting efferocytosis in macrophages

Abstract

Acute pancreatitis (AP) is associated with high mortality rates and is characterized by increased cell death of acinar cells, with the premature release and activation of digestive enzymes. In its acute phase, AP is accompanied by increased efferocytosis, to clear phagocytic apoptotic cells; annexin A1 (Anxa1) is key to efferocytosis, but its role in AP is still unknown. Here we show that Anxa1 deficiency abrogates the efferocytosis of pancreatic macrophages, resulting in the accumulation of apoptotic acinar cells and necrosis. Moreover, we showed that nano-liposomes loaded with Anxa1 mRNA alleviate AP pathology by suppressing the cGAMP-cGAS-STING pathway and restoring efferocytosis in macrophages. Our results reveal the crucial function of Anxa1 in the efferocytosis of macrophages during AP and illustrate a novel nanotechnology treatment approach for AP that may be of potential therapeutic value in humans.