Journal
MOLECULAR NUTRITION & FOOD RESEARCH
Volume 63, Issue 17, Pages -Publisher
WILEY
DOI: 10.1002/mnfr.201900144
Keywords
aldehyde dehydrogenases; dendritic cells; intestinal epithelial cells; peptide immunotherapy; Foxp3(+) ROR gamma t(+) T cells
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Funding
- Ministerio de Ciencia, Innovación y Universidades [AGL2017-88964-R] Funding Source: Medline
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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-gamma, 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-beta and the generation of Foxp3(+) ROR gamma t(+) cells. Conclusion OP induces the expression of aldehyde dehydrogenase enzymes in cells of the innate immune system and the development of Foxp3(+) ROR gamma t(+) T cells.
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