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


CONCLUSIONS
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.
Institute of Infection, Immunity and Inflammation, University of Glasgow, UK.
M
M
Komai-Koma
F
F
Brombacher
P N
PN
Pushparaj
B
B
Arendse
C
C
McSharry
J
J
Alexander
R
R
Chaudhuri
N C
NC
Thomson
A N J
AN
McKenzie
I
I
McInnes
F Y
FY
Liew
D
D
Xu
D000707:Anaphylaxis / Q000209:etiology / Q000276:immunology; D000818:Animals; D015550:Cell Degranulation / Q000276:immunology; D005434:Flow Cytometry; D006636:Histamine Release; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000187:drug effects; D000067596:Interleukin-33; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007378:Interleukins / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology*; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude
C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007378:Interleukins; D015847:Interleukin-4; D007073:Immunoglobulin E