Egg yolk augments type 2 immunity by activating innate cells
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Egg yolk augments type 2 immunity by activating innate cells Leticia Pérez‑Rodríguez1 · Mónica Martínez‑Blanco1 · Daniel Lozano‑Ojalvo1 · Elena Molina1 · Rosina López‑Fandiño1 Received: 9 May 2019 / Accepted: 13 December 2019 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Purpose Egg yolk (EY) may play a role during the sensitizing phase of egg allergy by exerting intestinal type 2-biasing effects. We aimed to identify the mechanism and role of EY in the induction of allergy to egg white (EW). Methods BALB/c mice were exposed intragastrically to EW, EY, or the mixture of EW:EY. In addition in vitro experiments were conducted with intestinal epithelial cells (IECs), dendritic cells (DCs), and T cells from naïve mice. Inflammatory and type 2 responses were evaluated. Results Administration of EW upregulated duodenal expression of factors that influence epithelial barrier integrity and function, such as Muc2 and Cldn2, type 2-promoting epithelial cytokines Il33 and Il25, DC genes Irf4 and Tnfsf4, and Th2cytokines Il14 and Il13. EW:EY further increased the expression of Il25 and Tslp in the duodenum, Il33 and Tslp in the jejunum, and the proportion of lamina propria group 2 innate immune cells (ILC2s) over EW alone. Moreover, it distinctively enhanced the expression of Irf4 and Cd1d1 in the Peyer’s patches (PPs), and of Il6, Il33, Gata3, and Il13, both in PPs and mesenteric lymph nodes. In co-cultures of DCs and T cells, EW:EY induced a higher expression of Gata3, Il4, and Il13, secretion of IL-13 and expansion of CD4+ T cells expressing ST2, the IL-33 receptor, than EW or EY added individually. Conclusion Co-administration of EY may promote sensitization to EW through activation of innate immune cells, such as IECs, DCs and ILC2s, that are central to the progress of allergies. Keywords Egg allergy · Egg white · Egg yolk · Dendritic cells · Group 2 innate immune cells · Intestinal epithelial cells
Introduction Even though food allergy is a relevant health issue because of its increasing prevalence, not much is known on the molecular mechanisms implicated in the sensing of food antigens and the triggering of allergic reactions bypassing the default tolerance state. The biological functionality of proteins, in particular proteolytic activity, is recognized as an important feature, but other biochemical properties can favour the detection of antigens by cells of the innate immune system, such as intestinal epithelial (IECs) or Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00394-019-02163-6) contains supplementary material, which is available to authorized users. * Rosina López‑Fandiño [email protected] 1
Instituto de Investigación en Ciencias de La Alimentación (CIAL, CSIC-UAM), Nicolás Cabrera 9, 28049 Madrid, Spain
dendritic cells (DCs), to initiate adaptive Th2 immunity and subsequent allergic reaction [1]. Furthermore, in addition to the intrinsic characteristics of food proteins, accompanying molecules f
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