Oral Immunotherapy with Egg Peptides Induces Innate and Adaptive Tolerogenic Responses

Scope: The mechanism through which peptide-based immunotherapy provides effective desensitization toward food allergy is investigated. Methods and results: 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-γ, 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-β and the generation of Foxp3⁺ RORγt⁺ cells. Conclusion: OP induces the expression of aldehyde dehydrogenase enzymes in cells of the innate immune system and the development of Foxp3⁺ RORγt⁺ T cells.