Interleukin-17A promotes IgE production in human B cells.
Recently the Th1/Th2 concept has been revised and Th17 cells have been implicated in allergy. Despite clear correlative evidence, the cellular and molecular basis for the connection between increased IL-17A and IgE in allergy has not been elucidated. Here we show using flow cytometry that allergic patients have higher numbers of IL-17A+ cells compared to nonallergic donors. The selective removal of IL-17A+ cells from peripheral blood mononuclear cells of allergic donors after an IL-17A secretion assay reduces IgE levels, whereas re-addition of recombinant IL-17A restores it, as measured by ELISA, showing their important functional implication for IgE production. In addition, IL-17A directly promotes the differentiation of IgE-secreting cells and IgE production upon anti-CD40/IL-4 costimulation, as shown by enzyme-linked immunospot technique and ELISA. IL-17A triggers rapid degradation of IκBα and subsequent translocation of NF-κB into the B-cell nucleus, followed by transcription of epsilon germ-line, activation-induced cytidine deaminase, and IFN regulatory factor 4, as analyzed by flow cytometry, western blot, and quantitative real-time RT-PCR, respectively. Our study shows that IL-17A+ cells promote IgE production and that IL-17A exerts its pro-allergic effect directly at the level of B cells. Therefore, IL-17A might be a target for the treatment of IgE-dependent diseases, including atopic dermatitis.
Milovanovic
Milena
M
Department of Dermatology and Allergy, Allergy-Center-Charité, CCM, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Drozdenko
Gennadiy
G
Weise
Christin
C
Babina
Magda
M
Worm
Margitta
M
D000328:Adult; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism; D007070:Immunoglobulin A / Q000276:immunology / Q000378:metabolism; D007073:Immunoglobulin E / Q000276:immunology* / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D052002:NF-kappa B p50 Subunit / Q000378:metabolism
C508717:IL17A protein, human; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D020381:Interleukin-17; D052002:NF-kappa B p50 Subunit; D007073:Immunoglobulin E