Targeting STING to disrupt macrophage-mediated adhesion in encapsulating peritoneal sclerosis

Encapsulating peritoneal sclerosis (EPS) is a life-threatening fibrotic condition characterized by severe abdominal adhesions, chronic inflammation, and significant morbidity. The lack of effective treatments for EPS stems from a limited understanding of its underlying mechanisms. In this study, we developed a modified mouse model of PD-induced EPS and investigated the role of the STING signaling pathway in disease progression. Our findings reveal that STING activation in peritoneal mesothelial cells significantly increases the secretion of the macrophage chemokine CCL2, leading to enhanced macrophage infiltration and the formation of pathological adhesions. Notably, pharmacological inhibition of STING using the inhibitor H151 effectively reduced macrophage infiltration and fibrosis, demonstrating its therapeutic potential in alleviating EPS. These results identify the STING pathway as a critical mediator of EPS pathogenesis and suggest that STING inhibitors could offer a promising therapeutic strategy to prevent or reverse EPS, particularly in clinical settings such as peritoneal dialysis. STING activation in peritoneal mesothelial cells promotes macrophage infiltration and peritoneal adhesion formation by inducing CCL2 secretion. This highlights the therapeutic potential of STING inhibitors in mitigating encapsulating peritoneal sclerosis.