IL-1 confers IgG-mediated protection against allergic anaphylaxis.

Abstract

Allergen immunotherapy (AIT) aims to redirect pathogenic IgE responses toward protective IgG antibodies. Interleukin-1 (IL-1) regulates humoral immunity, yet its role in shaping allergen-specific IgG responses remains unclear. We investigated whether IL-1 promotes allergen-specific IgG and protection against allergic anaphylaxis in murine models. Allergic sensitization and challenge were performed in wild-type (WT) and IL-1 receptor antagonist-deficient (IL-1Ra^-/^-) mice. IL-1β was blocked or co-administered with allergen during immunization. Anaphylaxis severity, allergen-specific antibody responses, and effector responsiveness were assessed. Serum and IgG transfer experiments and FcγRIIb blockade were conducted to determine mechanisms of protection. IL-1Ra^-/^- mice exhibited enhanced allergen-specific IgG responses and were protected from systemic anaphylaxis. In contrast, IL-1R1 blockade reduced IgG production and exacerbated anaphylactic responses. Preventive or therapeutic co-administration of IL-1β with allergen increased protective IgG levels and reduced anaphylaxis in systemic and food allergy models. Mechanistically, protection depended on IgG and FcγRIIb. Additionally, IL-1β upregulated FcγRIIb expression on mast cells, mediating short-term protection that was additive to IgG-dependent effects observed with combined treatment. IL-1 promotes IgG-dominant allergen-specific immune responses that protect against allergic anaphylaxis through FcγRIIb. Therapeutic administration of IL-1 may help overcome current limitations of AIT.