Anti-galectin-3 antibodies induce skin vascular inflammation via promoting local production of IL-1β in systemic lupus erythematosus.

Vascular inflammation could occur in all organs and tissues in patients with systematic lupus erythematosus (SLE), of which skin is the most frequent one. Our previous research identified anti-galectin-3 (Gal3) antibodies (Abs) as an important mediator of lupus cutaneous vasculopathy. Herein, we showed that anti-Gal3 Abs dysregulated the function of vascular endothelial cells with higher transcript levels of IL-1β and increased expression of mature IL-1β. The enhanced production of IL-1β secreted by endothelial cells was dependent on NLRP3 inflammasome. Intradermal injection of anti-Gal3 Abs in mice induced local inflammation with perivascular infiltration of T cells and neutrophils, which was inhibited by IL-1β blockade. Induction of anti-Gal3 Abs in circulation by immunization of Gal3 antigen not only led to histopathologic changes in the skin, including focal keratinocytes vacuolization and thickening of blood vessels, but also a systemic autoimmune phenotype that involves autoantibody production and kidney damage. Intriguingly, local overexpression of IL-1β was primarily associated with skin lesions but not with other internal organs in mice. Finally, we showed that the serum levels of IL-1β were comparable between SLE patients and healthy donors. Whilst the expression of IL-1β was enriched in local area with perivascular inflammation in lupus skin lesion compared to healthy normal skin. The results strongly suggest that IL-1β plays an important role in mediating anti-Gal3 Ab-induced skin vascular inflammation and raised the prospect for using IL-1β blocking therapies to treat lupus cutaneous damage.