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

Cell Immunol. 2022 Sep:379:104581. doi: 10.1016/j.cellimm.2022.104581. Epub 2022 Jul 29.

Abstract

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.

Keywords: Endotoxemia; Inflammation; LPS; Macrophage; Neutrophil; VISTA.

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Inflammation
  • Ligands
  • Lipopolysaccharides* / metabolism
  • Macrophages
  • Membrane Proteins
  • Mice
  • Neutrophils*

Substances

  • Cytokines
  • Ligands
  • Lipopolysaccharides
  • Membrane Proteins
  • Vsir protein, mouse