Abstract
BackgroundThe alarmin cytokines IL-25 and IL-33 are key promoters of type 2 inflammation. Basophils respond to alarmin cytokines, however the relationship of these cytokines with basophil activation and recruitment in human studies of allergic asthma has not been well characterized. This study investigated the effect of IL-25 and IL-33 on basophils in a model of allergic asthma.Methods10 mild allergic asthmatics underwent allergen and diluent inhalation challenges. Bone marrow aspirates were collected at pre-challenge and 24 h (h) post challenge. Peripheral blood and sputum samples were collected at pre-challenge, 7 h, and 24 h post-challenge to measure basophil expression of IL-17RB, ST2, and intracellular IL-25. Freshly isolated peripheral blood basophils from allergic donors were incubated overnight with IL-25 and IL-33, or sputum supernatant collected post-allergen to assess pro-inflammatory effects of mediators released in the airways.ResultsThere were increased percentage of basophils expressing IL-17RB, ST2, and intracellular IL-25 collected from bone marrow, peripheral blood, and sputum after allergen inhalation challenge. In vitro stimulation with IL-25 and IL-33 increased the percentage of basophils expressing intracellular type 2 cytokines and surface activation markers, and primed eotaxin-induced migratory potential of basophils, which was mediated directly through IL-17RB and ST2, respectively. Stimulation of basophils with sputum supernatants collected post-allergen challenge up-regulated the percentage of basophils expressing markers of activation and intracellular type 2 cytokines, which was reversed following blockade of the common β chain (βc).ConclusionsOur findings indicate that the alarmin cytokines IL-33 and IL-25 increase basophil activation and migratory potential, and may pose as a novel therapeutic targets for the treatment of allergic asthma.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-016-0321-z) contains supplementary material, which is available to authorized users.
Highlights
The alarmin cytokines IL-25 and IL-33 are key promoters of type 2 inflammation
We have previously reported that the percentage of basophils expressing surface activation markers, intracellular cytokines (IL-4; IL-13) and TSLPR, significantly increase in peripheral blood and sputum post-allergen inhalation in mild allergic asthmatics for up to 24 h [28]
Basophils have been identified as a source of IL-25 following IgE cross-linking [35], and we found intracellular IL-25 expression to be elevated within the periphery and sputum post-allergen, which may further contribute to Type 2 inflammation
Summary
The alarmin cytokines IL-25 and IL-33 are key promoters of type 2 inflammation. Basophils respond to alarmin cytokines, the relationship of these cytokines with basophil activation and recruitment in human studies of allergic asthma has not been well characterized. This study investigated the effect of IL-25 and IL-33 on basophils in a model of allergic asthma. Transgenic over-expression or administration of IL-25 and IL-33 generates airway eosinophilia, up-regulated Type 2 cytokine expression, elevated serum IgE, AHR and mucus hypersecretion [1,2,3,4,5,6]. Neutralization of IL-25 and IL-33 leads to reduction of airway inflammation, IgE levels, Type 2 cytokine expression, goblet cell hyperplasia, and AHR [7,8,9,10]. In human studies of allergic asthma, IL-33 and ST2 expression in serum, lung tissue and BALF have found to be higher in asthmatics compared
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