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 #x3c; 0.05) and IFNγ (p #x3c; 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 #x3c; 0.005) in T cells, while enhancing IL17 (p #x3c; 0.001) and IL10 (p #x3c; 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.
J Innate Immun

中文翻译：

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卵清蛋白诱导的上皮激活指导单核细胞衍生的树突状细胞指示 T 细胞中的 2 型炎症，该炎症受到 2'-岩藻糖基乳糖和 3-岩藻糖基乳糖的差异调节

过敏致敏始于上皮细胞激活，驱动树突状细胞 (DC) 指示辅助 T 2 (Th2) 细胞极化。食物过敏原会触发肠上皮细胞 (IEC) 激活。母乳寡糖可能通过塑造粘膜免疫反应来缓和过敏表型。我们通过将卵清蛋白 (OVA) 预暴露的 IEC 与单核细胞来源的 DC (OVA-IEC-DC) 相结合以及随后的 OVA 共培养，研究了过敏原暴露后的体外粘膜免疫发育。 -具有 Th 细胞的 IEC-DC。IECs 另外与 2'FL 或 3FL 一起预孵育。OVA 激活增加了 IEC 细胞因子的分泌。OVA-IEC-DC 指示Th 细胞分泌IL13 ( p #x3c; 0.05) 和 IFNγ ( p #x3c; 0.05)。2'FL 和 3FL 允许 OVA 诱导的上皮激活，但 2'FL-OVA-IEC-DC 促进炎症和调节性 T 细胞发育。3FL-OVA-IEC 降低 DC 中的 IL12p70 和 IL23，抑制T 细胞中的IL13 ( p #x3c; 0.005)，同时增强 IL17 ( p #x3c; 0.001) 和 IL10 ( p #x3c; 0.005)。这些结果表明，OVA在该模型中，通过激活 IEC 来驱动 Th2 型和 Th1 型免疫反应。2'FL 和 3FL 对 OVA-IEC 驱动的免疫效应有不同的影响。2'FL 通过 DC 增强炎症和调节反应，增强 T 细胞 OVA-IEC 整体免疫力。3FL-OVA-IEC-DC 沉默了 IL13，将平衡转向 IL17 和 IL10。该模型证明了 IEC 对 OVA Th2 型免疫的贡献。2'FL 和 3FL 在这个研究过敏致敏的新模型中调节 OVA 诱导的激活。
天然免疫杂志