Decreased expression of the immune checkpoint regulator VISTA on neutrophils correlates with disease activity in autoimmune uveitis

Abstract

Immune checkpoint V-domain Ig suppressor of T-cell activation (VISTA) exhibits distinct expression patterns and non-redundant immunoregulatory mechanisms in different autoimmune diseases. This study aims to investigate the expression of VISTA in patients with autoimmune uveitis and experimental autoimmune uveitis (EAU) mice, and explore its clinical significance and preliminary mechanisms in disease development. We found that VISTA expression on 12 subsets of peripheral blood immune cells was lower in autoimmune uveitis patients than in healthy volunteers, especially on neutrophils. The expression of neutrophil VISTA in active uveitis patients markedly increased when intraocular inflammation was ameliorated, indicating a significant correlation with disease activity. In vitro treatment of neutrophils from autoimmune uveitis patients with a VISTA antagonist markedly aggravated cell activation and neutrophil extracellular traps formation, whereas a VISTA agonist produced the opposite effect. Moreover, VISTA was constitutively expressed in the outer segments of retina in healthy mice, and decreased in EAU mice, reaching the lowest level of expression when the disease was at a peak stage. Taken together, this study investigates the relationship between neutrophil VISTA and the development of autoimmune uveitis, and provides new insights into the mechanisms and therapeutic roles of VISTA in autoimmune diseases.