Intestinal epithelial cells (IEC) release immunomodulatory galectins upon exposure to CpG DNA (mimicking bacterial triggers) and short-chain galacto- and long-chain fructo-oligosaccharides (GF). This study aims to investigate the immunomodulatory properties of 2'-fucosyllactose (2'-FL), a non-digestible oligosaccharide (NDO) abundantly present in human milk, using a co-culture model developed to study the crosstalk between IEC and innate and adaptive immune cells. IECs, co-cultured with αCD3/CD28-activated peripheral blood mononuclear cells (PBMC), were apically exposed to NDOs and CpG, washed and co-cultured with immature monocyte-derived dendritic cells (moDC). Subsequently, moDC were co-cultured with naïve CD4+ T-cells. In the presence of CpG, both 2'-FL or GF-exposed IEC enhanced Th1-type IFNγ and regulatory IL-10 secretion of PBMCs, compared to CpG alone, while Th2-type IL-13 was reduced. Both NDOs increased IEC-derived galectin-3, -4, -9 and TGF-β1 of CpG-exposed IEC. Only galectin-9 correlated with all modified immune parameters and TGF-β1 secretion. MoDCs exposed to 2'-FL and CpG-conditioned IEC instructed IFNγ and IL-10 secretion by CD4+ T-cells, suggesting the development of a regulatory Th1 response. These results reveal that 2'-FL and GF could contribute to the mucosal immune development by supporting the effect of microbial CpG DNA associated with the modulation of epithelial galectin and TGF-β1 secretion.

中文翻译：

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肠道上皮细胞暴露于2'-岩藻糖半乳糖和CpG增强半乳糖凝集素释放并指示树突状细胞驱动Th1和调节型免疫发育。

肠道上皮细胞（IEC）在暴露于CpG DNA（模仿细菌触发物）以及短链半乳糖和长链低聚果糖（GF）时释放免疫调节性半乳糖凝集素。这项研究旨在使用共同培养模型来研究IEC与先天和后天之间的串扰，研究2'-岩藻糖半乳糖（2'-FL）（在人乳中大量存在的一种非消化性低聚糖）的免疫调节特性。适应性免疫细胞。将与αCD3/ CD28激活的外周血单核细胞（PBMC）共培养的IEC顶端暴露于NDO和CpG，洗涤并与未成熟单核细胞衍生的树突状细胞（moDC）共培养。随后，将moDC与纯净的CD4 + T细胞共培养。在CpG存在下，两个2' 与单独的CpG相比，暴露于-FL或GF的IEC增强了PBMC的Th1型干扰素γ和调节性IL-10分泌，而Th2型IL-13降低了。两个NDO均增加了CpG暴露的IEC的IEC衍生的半乳凝素-3，-4，-9和TGF-β1。只有galectin-9与所有修饰的免疫参数和TGF-β1分泌相关。暴露于2'-FL和CpG条件的IEC的MoDC指示CD4 + T细胞分泌IFNγ和IL-10，这提示了Th1调节性反应的发展。这些结果表明2'-FL和GF可通过支持微生物CpG DNA与上皮半乳糖凝集素和TGF-β1分泌的调节相关的作用而有助于粘膜免疫发展。只有galectin-9与所有修饰的免疫参数和TGF-β1分泌相关。暴露于2'-FL和CpG条件的IEC的MoDC指示CD4 + T细胞分泌IFNγ和IL-10，这提示了Th1调节性反应的发展。这些结果表明2'-FL和GF可通过支持微生物CpG DNA与上皮半乳糖凝集素和TGF-β1分泌的调节相关的作用而有助于粘膜免疫发展。只有galectin-9与所有修饰的免疫参数和TGF-β1分泌相关。暴露于2'-FL和CpG条件的IEC的MoDC指示CD4 + T细胞分泌IFNγ和IL-10，这提示了Th1调节性反应的发展。这些结果表明2'-FL和GF可通过支持微生物CpG DNA与上皮半乳糖凝集素和TGF-β1分泌的调节相关的作用而有助于粘膜免疫发展。