Egg white peptide-based immunotherapy enhances vitamin A metabolism and induces RORγt+ regulatory T cells

Abstract

This study investigates the mechanism by which food peptides are more effective than intact allergens in providing desensitization against food allergy. BALB/c mice sensitized to egg white (EW) were subjected to oral immunotherapy (OIT) with intact and pepsin-hydrolysed EW (EP). Treatment with EP was superior to that with EW in terms of reduction of anaphylaxis and levels of specific antibodies. OIT with EP, but not with EW, modulated the microbiota by restoring the levels of some members of the order Clostridiales (clusters IV and XIVa) that were affected by sensitization. Mice treated with EP exhibited upregulated intestinal expression of Il22 and Muc2, which encode for factors that contribute to reinforce the epithelial barrier function, as well as Aldh1a1, Aldh1a2, Csf2 and Tfgb1, that take part in the conversion of vitamin A into retinoic acid. Tolerance induced by EP paralleled the development of Foxp3+ cells that simultaneously expressed RORγt.

Keywords

• Food allergy
• Egg-peptide immunotherapy
• Microbiota
• Retinoic acid
• RORγt
• Regulatory T cells