Interleukin-17A Promotes IgE Production in Human B Cells

Abstract

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.

Total and Antigen- (Fungi, Mites and Staphylococcal Enterotoxins) Specific IgEs in Nasal Polyps Is Related to Local Eosinophilic Inflammation

“…Allergen-driven class switching to IgE was confirmed in the nasal mucosa [22,23]. A recent study indicated that both Th17 cells and IL-17 promote IgE production and exert direct proallergic effects at the level of B cells [24]. IL-17 expression was associated with allergic diseases, such as asthma [25] and CRSwNP comorbid with asthma [26].…”

Atopic dermatitis - from new pathophysiologic insights to individualized therapy

“…The observation that IL-17-induced upregulation of HBD-2 by keratinocytes was abolished by IL-4, and IL-13 might explain the failure to clear S. aureus in AD (95). IL-17 was reported to promote IgE production in B cells (96). These observations point to an important role of Th17 cells in the pathogenesis of AD.…”

High Serum IgE Concentration in Patients with Psoriasis

“…In addition, IgE promotes the autocrine production of IL-6 in human lung mast cells [27]. Recently, a study showed that IgE-secreting cells differentiation and IgE production could be directly promoted by IL-17 [28]. We wondered that whether TNF-α, IL-6 or IL-8 could be, just like IL-17, involved in the regulation of IgE in psoriasis, so we measured the serum levels of TNF-α, IL-6 and IL-8 in patients with psoriasis and performed correlation analysis.…”