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长链和中链脂肪酸对肠道树突状细胞功能的差异调节

Differential modulation in the functions of intestinal dendritic cells by long- and medium-chain fatty acids.

作者信息

Tsuzuki Yoshikazu, Miyazaki Jyunichi, Matsuzaki Koji, Okada Yoshikiyo, Hokari Ryota, Kawaguchi Atsushi, Nagao Shigeaki, Itoh Kazuro, Miura Soichiro

机构信息

Second Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, 359-8513, Japan.

出版信息

J Gastroenterol. 2006 Mar;41(3):209-16. doi: 10.1007/s00535-005-1747-0.

Abstract

BACKGROUND

Although dendritic cells (DCs) play significant roles in intestinal immune responses, little is known regarding the direct effects of luminal foods on DC functions in the intestinal mucosa. In this study, we examined the effects of fatty acids (FAs) with various chain length on the phagocytic function, antigen presentation, and chemotaxis of intestinal DCs.

METHODS

DCs obtained from the thoracic duct lymph of mesenteric lymphadenectomized rats were cultured with long [arachidonic acid (AA) or oleic acid] or medium (octanoic acid) chain FAs with interleukin-4 and granulocyte macrophage-colony stimulating factor. Tumor necrosis factor-alpha was added in the maturation group. Phagocytic function was examined by the intake of fluorescent microbeads. The expression of cell surface molecules was determined by immunocytochemistry or fluorescence-activated cell sorting (FACS). Antigen presentation ability was evaluated by coincubating keyhole limpet hemocyanin (KLH)-sensitized spleen lymphocytes and KLH-pulsed DCs. Migratory ability of DCs toward the chemokines CC chemokine ligand (CCL) 20 and CCL21 was also assessed.

RESULTS

There was a maturation-induced decrease in phagocytic function, and an increased expression of major histocompatibility complex (MHC) class II molecules. Exposure of DCs to both long- and medium-chain FAs maintained phagocytic ability. The expression of MHC class II molecules was significantly suppressed only by long-chain FAs. The expression of costimulatory factors was suppressed only by AA. Long- but not medium-chain FAs suppressed the antigen presentation ability of DCs induced by maturation. Chemotactic ability of mature DCs toward CCL21 was abrogated only by long-chain FAs.

CONCLUSIONS

The data suggest that intraluminal exposure to long- and medium-chain FAs may differentially modulate the immune functions of intestinal DCs.

摘要

背景

尽管树突状细胞(DCs)在肠道免疫反应中发挥重要作用,但关于肠腔食物对肠道黏膜中DC功能的直接影响却知之甚少。在本研究中,我们检测了不同链长的脂肪酸(FAs)对肠道DC吞噬功能、抗原呈递及趋化性的影响。

方法

从肠系膜淋巴结切除大鼠的胸导管淋巴中获取DCs,将其与长链[花生四烯酸(AA)或油酸]或中链(辛酸)脂肪酸、白细胞介素-4和粒细胞巨噬细胞集落刺激因子共同培养。成熟组添加肿瘤坏死因子-α。通过摄取荧光微珠检测吞噬功能。通过免疫细胞化学或荧光激活细胞分选(FACS)测定细胞表面分子的表达。通过将钥孔戚血蓝蛋白(KLH)致敏的脾淋巴细胞与KLH脉冲DCs共同孵育来评估抗原呈递能力。还评估了DCs对趋化因子CC趋化因子配体(CCL)20和CCL21的迁移能力。

结果

成熟诱导吞噬功能下降,主要组织相容性复合体(MHC)II类分子表达增加。DCs暴露于长链和中链脂肪酸均可维持吞噬能力。仅长链脂肪酸显著抑制MHC II类分子的表达。共刺激因子的表达仅被AA抑制。长链而非中链脂肪酸抑制成熟诱导的DCs抗原呈递能力。成熟DCs对CCL21的趋化能力仅被长链脂肪酸消除。

结论

数据表明,肠腔内暴露于长链和中链脂肪酸可能对肠道DC的免疫功能产生不同的调节作用。

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