Ovalbumin-derived peptides activate retinoic acid signalling pathways and induce regulatory responses through toll-like receptor interactions

Mónica Martínez-Blanco, Leticia Pérez-Rodríguez, Daniel Lozano-Ojalvo, Elena Molina, Rosina López-Fandiño

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

This study investigates the potential of a hydrolysate of ovalbumin with pepsin (OP) to preclude Th2-type immunity by the enhancement of tolerogenic dendritic cells (DCs) and regulatory T (Treg) cells. Through Toll-like receptor (TLR) stimulation, OP enhances the retinoic acid pathway on DCs by means of the induction of aldehyde dehydrogenase enzymes and transforming growth factor beta (TGF-β), and it confers upon DC the ability to upregulate interleukin 10 (IL-10) as well as other tolerance-promoting mediators downstream of TRL signalling, such as IL-27, IL-33, Notch ligands, OX40L, and the transcription factors IRF4 and IRF8. OP-conditioned DCs induce the expansion of Foxp3+ and Tr1 cells in co-culture with CD4+ T cells. Furthermore, OP directly conditions CD4+ T cells from naïve mice, without the mediation of DCs, to express aldehyde dehydrogenase (ALDH) enzymes and, in the presence of the Th2 cytokine IL-4 and exogenous TGF-β, it enhances Foxp3 expression. It is noteworthy that, on CD4+ T cells isolated from egg-allergic mice, OP significantly enriches the levels of Foxp3+ and Foxp3+ RORγt+ CD4+ T cells. In conclusion, we show that food peptides may work, analogously to microbial-driven signals, through TLRs, to promote a tolerogenic phenotype on cells of the innate and adaptive immune system, a property that is further enhanced in the context of a Th2 cytokine-rich environment.

Original languageEnglish
Article number831
JournalNutrients
Volume12
Issue number3
DOIs
StatePublished - Mar 2020
Externally publishedYes

Keywords

  • Dendritic cells
  • Peptide immunotherapy
  • Regulatory T cells
  • Retinoic acid
  • Toll like receptors

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