IL-1 confers IgG-mediated protection against allergic anaphylaxis.
Publisher DOI
PubMed ID
42526605
Abstract
Background
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.Objective
We investigated whether IL-1 promotes allergen-specific IgG and protection against allergic anaphylaxis in murine models.Methods
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.Results
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.Conclusion
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.
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.Objective
We investigated whether IL-1 promotes allergen-specific IgG and protection against allergic anaphylaxis in murine models.Methods
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.Results
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.Conclusion
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.
Date Issued
2026-07-29
Publication Type
Article
Subject(s)
Subjects
Adjuvant
•
Allergen immunotherapy (AIT
•
FcγRIIb
•
IgE
•
Immune Deviation
•
Interleukin-1
•
SIT)
•
allergy
•
antibodies
•
basophils
•
mast cells
Language(s)
en
Author(s)
Issa, Mohammad | |
Belbezier, Aude | |
Vaineau, Romain | |
Miguez, Jennifer | |
Fourcade, Gwladys | |
Vigneron, James | |
Tchitchek, Nicolas | |
Graff-Dubois, Stephanie | |
Bellier, Bertrand | |
Klatzmann, David |
Journal
Journal of Allergy and Clinical Immunology
Publisher
Elsevier
ISSN
1097-6825
0091-6749
Access(Rights)
embargo