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寡糖 6'-唾液乳糖、2'-岩藻糖乳糖或半乳糖寡糖不会直接调节人树突状细胞的分化或成熟。

The oligosaccharides 6'-sialyllactose, 2'-fucosyllactose or galactooligosaccharides do not directly modulate human dendritic cell differentiation or maturation.

机构信息

Cell Biology and Immunology group, Wageningen University, Wageningen, the Netherlands.

FrieslandCampina, Amersfoort, the Netherlands.

出版信息

PLoS One. 2018 Jul 10;13(7):e0200356. doi: 10.1371/journal.pone.0200356. eCollection 2018.

Abstract

Breast milk plays an important role in immune development in early life and protects against diseases later in life. A wide range of the beneficial effects of breast milk are attributed to human milk oligosaccharides (HMOs) as well as components such as vitamin D3 (VitD3) or TGFβ. One mechanism by which HMOs might contribute to immune homeostasis and protection against disease is the induction of a local tolerogenic milieu. In this study we investigated the effect of the HMOs 6'-sialyllactose (6'SL) and 2'-fucosyllactose (2'FL) as well as prebiotic galactooligosaccharides (GOS) on DC differentiation and maturation. Isolated CD14+ monocytes were cultured for six days in the presence of GM-CSF and IL-4 with or without 6'SL, 2'FL, GOS, VitD3 or TGFβ. Additionally, immature VitD3DC, TGFβDC and moDC were used as different DC types to investigate the effect of 6'SL, 2'FL and GOS on DC maturation. Surface marker expression and cytokine production was measured by flow cytometry and cytometric bead array, respectively. Unlike TGFβ and vitD3, the oligosaccharides 6'SL, 2'FL and GOS did not influence DC differentiation. Next, we studied the effect of 6'SL, 2'FL and GOS on maturation of moDC, VitD3DC and TGFβDC that showed different profiles of HMO-binding receptors. 6'SL, 2'FL and GOS did not modulate LPS-induced maturation, even though their putative receptors were present on the different DCs types. Thus, whereas VitD3 and TGFβ halt DC differentiation, which results in phenotypically distinct tolerogenic DCs, 6'SL, 2'FL and GOS do not alter DC differentiation or maturation of in vitro differentiated DC types.

摘要

母乳在婴儿早期的免疫发育中起着重要作用,并能预防日后的疾病。母乳的许多有益作用归因于人乳寡糖(HMOs)以及维生素 D3(VitD3)或 TGFβ 等成分。HMO 可能通过诱导局部耐受环境来促进免疫稳态和预防疾病的一种机制。在这项研究中,我们研究了 HMO 6'-唾液酸乳糖(6'SL)和 2'-岩藻糖基乳糖(2'FL)以及益生元半乳糖低聚糖(GOS)对 DC 分化和成熟的影响。分离的 CD14+单核细胞在 GM-CSF 和 IL-4 的存在下培养六天,有或没有 6'SL、2'FL、GOS、VitD3 或 TGFβ。此外,还使用不成熟的 VitD3DC、TGFβDC 和 moDC 作为不同的 DC 类型,研究 6'SL、2'FL 和 GOS 对 DC 成熟的影响。通过流式细胞术和细胞计数珠阵列分别测量表面标志物表达和细胞因子产生。与 TGFβ 和 VitD3 不同,寡糖 6'SL、2'FL 和 GOS 不影响 DC 分化。接下来,我们研究了 6'SL、2'FL 和 GOS 对 moDC、VitD3DC 和 TGFβDC 成熟的影响,这些 DC 具有不同的 HMO 结合受体谱。6'SL、2'FL 和 GOS 并未调节 LPS 诱导的成熟,尽管它们的假定受体存在于不同的 DC 类型上。因此,尽管 VitD3 和 TGFβ 阻止 DC 分化,导致表型上不同的耐受 DC,但 6'SL、2'FL 和 GOS 不会改变体外分化的 DC 类型的 DC 分化或成熟。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4e0/6039038/2b1c687e7d91/pone.0200356.g001.jpg

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