VISTA mediated anti-inflammatory function in monocyte-derived macrophages for treatment of septic ARDS 4357

Abstract Description Acute respiratory distress syndrome (ARDS), a common complication seen in septic patients, is characterized by lung epithelial and endothelial barrier dysfunction leading to pulmonary edema and organ failure. Currently, ARDS has a 30-40% mortality rate with no effective pathological-pharmacological based treatment available. Bone marrow-derived macrophages (BMDMs) contribute to the immune dysfunction and organ damage experienced in ARDS patients when they are recruited into affected tissues and adapt a pro-inflammatory phenotype. The negative checkpoint regulator V-domain Ig suppressor of T-cell Activation (VISTA) from the B7/CD28 superfamily is expressed across the hematopoietic compartment and has been shown to promote an anti-inflammatory protective effect on survival in sepsis mouse models. Using an established indirect ARDS animal model, characterized by an initial insult of fixed pressure hemorrhagic shock followed by polymicrobial sepsis through cecal ligation puncture, the therapeutic potential of VISTA treatment was examined. Bone marrow samples from iARDS mice were harvested and VISTA expression and function from polarized BMDMs was characterized with flow cytometry and functional assays. Preliminary data has revealed an impaired reduction of IL-6 in iARDS BMDMs polarized with IL-4 when compared to their sham controls. Our results examine the anti-inflammatory function mediated by VISTA in monocyte-derived macrophages as a potential treatment of septic ARDS. Funding Sources Supported by NIH R35 GM118097 Topic Categories Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)