Basophil-derived interleukin-4 promotes epicutaneous antigen sensitization concomitant with the development of food allergy

Publication date: Available online 6 April 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Maryam Hussain, Loïc Borcard, Kevin P. Walsh, Maria Pena Rodriguez, Christoph Mueller, Brian S. Kim, Masato Kubo, David Artis, Mario Noti
BackgroundExaggerated TSLP production and infiltration of basophils are associated with the pathogenesis of atopic dermatitis (AD), a recognized risk factor for the development of food allergies. While TSLP and basophils have been implicated to promote food-induced allergic disorders in response to epicutaneous sensitization, the mechanisms by which TSLP-elicited basophils guide the progression of allergic inflammation in the skin to distant mucosal sites such as the gastrointestinal tract are poorly understood.ObjectiveWe sought to test the role of basophil-intrinsic IL-4 production in TH2 sensitization to food antigens in the skin and effector food allergic responses in the gut.MethodsMice were epicutaneously sensitized with ovalbumin on an AD-like skin lesion, followed by intra-gastric antigen challenge to induce IgE-mediated food allergy. The requirement for basophil-derived IL-4 production for TH2 polarization and the pathogenesis of IgE-mediated food allergy was assessed in vitro by co-culture experiments with naïve T cells and in vivo using IL-4 3'UTR mice that selectively lack IL-4 production in basophils.ResultsEpicutaneous food antigen sensitization is associated with the infiltration of IL-4 competent innate immune cells to the skin with basophils and eosinophils representing the predominant populations. In contrast to basophils, absence of eosinophils did not alter disease outcome. Co-culture of IL-4 competent basophils together with dendritic cells and naïve T cells was sufficient to promote TH2 polarization in an IL-4 dependent manner in vitro, while absence of basophil-intrinsic IL-4 production in vivo was associated with reduced food allergic responses.ConclusionTSLP-elicited basophils promote epicutaneous sensitization to food antigens and subsequent IgE-mediated food allergy via IL-4. Strategies to target the TSLP-basophil-IL4 axis in patients with AD may lead to innovative therapies that can prevent the progression of allergies to distant mucosal sites.



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