Ovalbumin-Induced Epithelial Activation Directs Monocyte-Derived Dendritic Cells to Instruct Type 2 Inflammation in T Cells Which Is Differentially Modulated by 2′-Fucosyllactose and 3-Fucosyllactose

Abstract

Allergic sensitization starts with epithelial cell activation driving dendritic cells (DCs) to instruct T helper 2 (Th2) cell polarization. Food allergens trigger intestinal epithelial cell (IEC) activation. Human milk oligosaccharides may temper the allergic phenotype by shaping mucosal immune responses.We investigated in vitro mucosal immune development after allergen exposure by combining ovalbumin (OVA)-preexposed IEC with monocyte-derived DCs (OVA-IEC-DCs) and subsequent coculture of OVA-IEC-DCs with Th cells. IECs were additionally preincubated with 2′FL or 3FL.OVA activation increased IEC cytokine secretion. OVA-IEC-DCs instructed both IL13 (p < 0.05) and IFNγ (p < 0.05) secretion from Th cells. 2′FL and 3FL permitted OVA-induced epithelial activation, but 2′FL-OVA-IEC-DCs boosted inflammatory and regulatory T-cell development. 3FL-OVA-IEC lowered IL12p70 and IL23 in DCs and suppressed IL13 (p < 0.005) in T cells, while enhancing IL17 (p < 0.001) and IL10 (p < 0.005).These results show that OVA drives Th2- and Th1-type immune responses via activation of IECs in this model. 2′FL and 3FL differentially affect OVA-IEC-driven immune effects. 2′FL boosted overall T-cell OVA-IEC immunity via DC enhancing inflammatory and regulatory responses. 3FL-OVA-IEC-DCs silenced IL13, shifting the balance towards IL17 and IL10.This model demonstrates the contribution of IEC to OVA Th2-type immunity. 2′FL and 3FL modulate the OVA-induced activation in this novel model to study allergic sensitization.

Keywords

• allergic sensitization
• food allergy
• human milk oligosaccharides
• in vitro models
• mucosal immunity