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Oral Immunotherapy with Egg Peptides Induces Innate and Adaptive Tolerogenic Responses

Lozano-Ojalvo, D;Martnez-Blanco, M;Prez-Rodrguez, L;Molina, E;Lpez-Fandio, R;

The mechanism through which peptide-based immunotherapy provides effective desensitization toward food allergy is investigated. Ex vivo experiments are conducted with intestinal epithelial cells (IECs), dendritic cells (DCs), and T cells from mice sensitized to egg white (EW) and either left untreated or tolerized by the oral administration of a hydrolysate of ovalbumin with pepsin (OP). IECs from EW-sensitized mice upregulate Il33 and Tslp to a higher extent than those from tolerized mice and induce bone marrow (BM)-DCs to express Tnfsf4 and produce pro-inflammatory cytokines. On the other hand, incubation with OP upregulates Aldh1a1 in IEC cultures and BM-DCs conditioned with supernatants of OP-pulsed IECs also overexpress Aldh1a2 and Tgfb1. DCs from tolerized mice, in co-culture with CD4+ T cells from sensitized mice, reduce the secretion of IL-5, IFN-, and IL-17, following stimulation with EW, to a level similar than DCs from sham-sensitized mice. Furthermore, incubation with OP of DCs and CD4+ T cells, regardless of the mouse sentitization status, promotes the secretion of TGF- and the generation of Foxp3+ RORt+ cells. OP induces the expression of aldehyde dehydrogenase enzymes in cells of the innate immune system and the development of Foxp3+ RORt+ T cells. 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.