Cell Biology and Immunology group, Wageningen University & Research, Zodiac building 122, de Elst 1, 6708 WD, Wageningen, The Netherlands.
FrieslandCampina, Stationsplein 4, 3818 LE, Amersfoort, T he Netherlands.
Glycobiology. 2018 Mar 1;28(3):126-130. doi: 10.1093/glycob/cwx106.
The human milk oligosaccharide 3'-sialyllactose (3'SL) has previously been shown to activate murine dendritic cells (DC) in a Toll-like receptor (TLR) 4-mediated manner ex vivo. In this study we aimed to investigate whether 3'SL has similar immunomodulatory properties on human DC. 3'SL was shown to induce NF-κB activation via human TLR4. However, LPS was detected in the commercially obtained 3'SL from different suppliers. After the removal of LPS from 3'SL, we studied its ability to modify DC differentiation in vitro. In contrast to LPS and 3'SL, LPS-free 3'SL did not induce functional and phenotypical changes on immature DC (iDC). iDC that were differentiated in the presence of LPS or 3'SL showed a semi-mature phenotype (i.e., fewer CD83+CD86+ DC), produced IL-10 and abrogated IL-12p70 and tumor necrosis factor-alpha levels upon stimulation with several TLR ligands. Differentiation into these tolerogenic DC was completely abrogated by LPS removal from 3'SL. In contrast to previous reports in mice, we found that LPS-free 3'SL does not activate NF-κB via human TLR4. In conclusion, removing LPS from (oligo)saccharide preparations is necessary to study their potential immunomodulatory function.
人乳寡糖 3'-唾液酸乳糖（3'SL）先前已被证明可通过 Toll 样受体（TLR）4 介导的方式在体外激活鼠树突状细胞（DC）。在这项研究中，我们旨在研究 3'SL 是否对人 DC 具有类似的免疫调节特性。3'SL 被证明可通过人 TLR4 诱导 NF-κB 激活。然而，在不同供应商提供的商业获得的 3'SL 中检测到 LPS。在从 3'SL 中去除 LPS 后，我们研究了其在体外修饰 DC 分化的能力。与 LPS 和 3'SL 相反，无 LPS 的 3'SL 不会诱导未成熟 DC（iDC）的功能和表型变化。在 LPS 或 3'SL 存在下分化的 iDC 表现出半成熟表型（即，更少的 CD83+CD86+ DC），产生 IL-10 并抑制 TLR 配体刺激后 IL-12p70 和肿瘤坏死因子-α水平。从 3'SL 中去除 LPS 完全消除了这些耐受性 DC 的分化。与先前在小鼠中的报道相反，我们发现无 LPS 的 3'SL 不会通过人 TLR4 激活 NF-κB。总之，从（寡）糖制剂中去除 LPS 对于研究其潜在的免疫调节功能是必要的。
