The role of VISTA engagement in limiting neutrophil-mediated inflammation

A growing body of evidence suggests that VISTA, an immune checkpoint inhibitory receptor, plays a central role in the regulation of innate immunity in the settings of inflammatory diseases and cancer. Neutrophils are among the cells that have the highest membrane density of surface VISTA. Targeting VISTA on neutrophils with an agonist antibody resulted in a striking reduction in their LPS-induced peripheral accumulation. Fc receptor engagement was required for anti-VISTA antibody to mediate its effects on neutrophils. Concomitant with reduced peripheral neutrophil cell numbers, anti-VISTA antibody treatment increased neutrophil cell death in the liver. In a murine model of neutrophil-mediated arthritis, agonist anti-VISTA antibody treatment ameliorated disease severity, which was associated with reduced myeloperoxidase activity in the joints. These studies add to a growing spectrum of negative regulatory functions that VISTA performs in controlling inflammation through the innate and adaptive arms of the immune system that has implications for translation into the clinic.