VISTA as a ligand downregulates LPS-mediated inflammation in macrophages and neutrophils.

VISTA has been proposed to function both as a ligand and a receptor to dampen immune responses, although the role of VISTA as a ligand on myeloid cells has been largely ignored. We observed that a VISTA receptor is rapidly expressed on the surface of macrophages and neutrophils upon exposure to lipopolysaccharides (LPS). Importantly, treating LPS-stimulated macrophages and neutrophils ex vivo with a high-avidity agonist of the VISTA receptor (VISTA.COMP) results in the downregulation of pro-inflammatory cytokines and the increased expression of immunoregulatory genes. Finally, the in vivo administration of VISTA.COMP attenuated the rise in circulating TNFα, IL-6, and IL-12p40 in LPS-treated mice.