Interleukin-33 amplifies IgE synthesis and triggers mast cell degranulation via interleukin-4 in naïve mice

Komai-Koma, M. et al. (2012) Interleukin-33 amplifies IgE synthesis and triggers mast cell degranulation via interleukin-4 in naïve mice. Allergy, 67(9), pp. 1118-1126. (doi: 10.1111/j.1398-9995.2012.02859.x) (PMID:22702477) (PMCID:PMC3660789)

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Background: The regulation and function of IgE in healthy individuals and in antigen-naïve animals is not well understood. IL-33 administration increases serum IgE in mice with unknown mechanism. We tested the hypothesis that IL-33 provides an antigen-independent stimulus for IgE production and mast cell degranulation. Methods: IL-33 was administered to naïve wild-type (WT), nude and ST2−/−, IL-4−/−, IL4Rα−/− and T-or B-cell-specific IL-4Rα−/− mice. IgEand cytokines were quantified by ELISA. T- and B-lymphocyte numbers and CD40L expression were determined by flow cytometry. Anaphylaxis was measured by temperature, mast cell degranulation and histamine release. Results: IL-33 enhanced IgE production in naïve WT, T-IL-4Rα−/− but not in ST2−/−, IL-4−/−, IL-4Rα−/− or B-cell-specific IL-4Rα−/− mice, demonstrating IL-33 specificity and IL-4 dependency. Moreover, IL-4 was required for IL-33-induced B-cell proliferation and T-cell CD40L expression, which promotes IgE production. IL-33-induced IL-4 production was mainly from innate cells including mast cells and eosinophils. IL-33 increased mast cell surface IgE and triggered degranulation and systemic anaphylaxis in allergen-naïve WT but not in IL-4Rα−/− mice. Conclusion: IL-33 amplifies IgE synthesis and triggers anaphylaxis in naïve mice via IL-4, independent of allergen. IL-33 may play an important role in nonatopic allergy and idiopathic anaphylaxis.

Item Type:Articles
Additional Information:This study received financial support fromArthritis Research, UK, the MedicalResearch Council, UK, and the Wellcome Trust.
Glasgow Author(s) Enlighten ID:Liew, Prof Foo and McInnes, Professor Iain and Xu, Dr Damo and Thomson, Professor Neil and Komai-Koma, Dr Mousa and Chaudhuri, Dr Rekha and McSharry, Dr Charles
Authors: Komai-Koma, M., Brombacher, F., Pushparaj, P. N., Arendse, B., McSharry, C., Alexander, J., Chaudhuri, R., Thomson, N. C., McKenzie, A. N. J., McInnes, I., Liew, F. Y., and Xu, D.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Allergy
ISSN (Online):1398-9995
Published Online:15 June 2012
Copyright Holders:Copyright © 2012 John Wiley and Sons.
First Published:First published in Allergy 67:1118-1126

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
486461The role of IL-35 in infection and inflammationFoo LiewMedical Research Council (MRC)G0801198III -IMMUNOLOGY