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膳食不可消化低聚糖和 M-16V 通过靶向树突状细胞成熟抑制肠道过敏炎症。

Dietary, nondigestible oligosaccharides and M-16V suppress allergic inflammation in intestine via targeting dendritic cell maturation.

机构信息

Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands; and

Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands; and.

出版信息

J Leukoc Biol. 2017 Jul;102(1):105-115. doi: 10.1189/jlb.3A0516-236R. Epub 2017 May 11.

Abstract

Dietary intervention with short-chain galacto-oligosaccharides (scGOS), long-chain fructo-oligosaccharides (lcFOS) and M-16V () (GF/) suppresses food allergic symptoms in mice, potentially via intestinal epithelial cell (IEC)-derived galectin-9. Furthermore, in vitro studies showed galacto- and fructo-oligosaccharides (GF) to enhance the immunomodulatory capacity of a TLR9 ligand representing bacterial CpG DNA when exposed to IEC. In this study, we investigated whether GF/ modulates dendritic cells (DCs) and subsequent Th2 and regulatory T cell (T) frequency in the small intestinal lamina propria (SI-LP). BALB/c mice were fed GF/ during oral OVA sensitization. DC and T cell phenotype were determined in SI-LP mononuclear cells using flow cytometry. Murine bone marrow-derived DCs (BMDCs) were exposed to recombinant galectin-9 or human monocyte-derived DCs (moDCs) and were cultured in IEC-conditioned medium from GF and TLR9 ligand-exposed HT-29 cells. GF/ reduced allergic symptoms and enhanced serum galectin-9 levels, while suppressing activation, restoring phagocytic capacity, and normalizing CD103 expression of SI-LP DCs of OVA-allergic mice. In vitro, galectin-9 suppressed LPS-induced activation markers and cytokine secretion by BMDCs, and IEC-conditioned medium suppressed moDC activation in a galectin-9-dependent manner. Besides suppression of SI-LP DC activation, dietary GF/ also lowered the frequency of activated Th2 cells, while enhancing T in the SI-LP of OVA-allergic mice compared to the control diet. Dietary intervention with GF/ enhances galectin-9 and suppresses allergic symptoms of OVA-allergic mice in association with reduced intestinal DC and Th2 activation and increased T frequency in these mice.

摘要

饮食干预短链半乳糖寡糖(scGOS)、长链果糖寡糖(lcFOS)和 M-16V()(GF/)可抑制食物过敏小鼠的过敏症状,可能通过肠上皮细胞(IEC)衍生的半乳糖凝集素-9(Galectin-9)实现。此外,体外研究表明,当暴露于 IEC 时,半乳糖和果糖寡糖(GF)可增强 TLR9 配体(代表细菌 CpG DNA)的免疫调节能力。在这项研究中,我们研究了 GF/是否调节了小肠固有层(SI-LP)中的树突状细胞(DC)和随后的 Th2 和调节性 T 细胞(T)频率。BALB/c 小鼠在口服 OVA 致敏期间接受 GF/喂养。通过流式细胞术测定 SI-LP 单核细胞中的 DC 和 T 细胞表型。将重组半乳糖凝集素-9或人单核细胞衍生的树突状细胞(moDC)暴露于 GF 和 TLR9 配体暴露的 HT-29 细胞的 IEC 条件培养基中,并培养骨髓来源的 DC(BMDC)。GF/减少了过敏症状并增加了血清半乳糖凝集素-9 水平,同时抑制了 OVA 过敏小鼠的 SI-LP DC 的活化、恢复吞噬能力并使其 CD103 表达正常化。在体外,半乳糖凝集素-9抑制了 BMDC 的 LPS 诱导的活化标志物和细胞因子分泌,IEC 条件培养基以半乳糖凝集素-9 依赖的方式抑制了 moDC 的活化。除了抑制 SI-LP DC 的活化外,GF/饮食还降低了 OVA 过敏小鼠 SI-LP 中活化的 Th2 细胞的频率,同时增加了 T 细胞的频率,与对照饮食相比。GF/饮食干预增强了 Galectin-9 并抑制了 OVA 过敏小鼠的过敏症状,与这些小鼠的肠道 DC 和 Th2 活化减少以及 T 频率增加有关。

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