Oxidized galectin-1 in SLE fails to bind the inhibitory receptor VSTM1 and increases reactive oxygen species levels in neutrophils.

ABSTRACT: Inhibitory immune receptors set thresholds for immune cell activation, and their deficiency predisposes a person to autoimmune responses. However, the agonists of inhibitory immune receptors remain largely unknown, representing untapped sources of treatments for autoimmune diseases. Here, we show that V-set and transmembrane domain-containing 1 (VSTM1) is an inhibitory receptor and that its binding by the competent ligand soluble galectin-1 (Gal1) is essential for maintaining neutrophil viability mediated by downregulated reactive oxygen species production. However, in patients with systemic lupus erythematosus (SLE), circulating Gal1 is oxidized and cannot be recognized by VSTM1, leading to increased intracellular reactive oxygen species levels and reduced neutrophil viability. Dysregulat

SUBMITTER: Jiang X 

PROVIDER: S-EPMC10616122 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature