Gastrointestinal dendritic cells promote Th2 skewing via OX40L
Gastrointestinal dendritic cells promote Th2 skewing via OX40L
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DOI：
10.4049/jimmunol.180.7.4441
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发表时间：
2008-04-01
影响因子：
4.4
通讯作者：
Berin, M. Cecilia
中科院分区：
文献类型：
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作者：
Blazquez, Ana Belen;Berin, M. Cecilia
小鼠可以通过口服佐剂霍乱毒素(CT)来对食物蛋白致敏，这样当它们再次受到致敏变应原的攻击时，它们就会发生过敏反应。相比之下，单独喂食AGS会导致口服耐受性。我们的目的是明确胃肠道树突状细胞(DC)参与肠道对CT过敏反应的耐受性偏离的机制。给BALB/c小鼠灌胃CT或PBS。用流式细胞仪检测CT对肠系膜淋巴结DC亚群的影响。用从PBS或CT喂养的小鼠的MLN分离的DC进行AG递呈分析，使用OVA特异性的CD4(+)T细胞作为应答细胞。实时荧光定量聚合酶链式反应检测mln树突状细胞的基因表达，中和抗体检测OX40配体(OX40L)在Th2偏斜中的作用。口服CT可诱导MLN中CD11c(+)细胞总数增加。CT诱导CD11c(+)、CD11b(-)、CD8α(-)DC亚群选择性迁移增加，所有DC亚群均成熟。DC体内成熟可促进T细胞增殖和细胞因子分泌。口服CT诱导mln DC上调Jagge-2和OX40L的表达。中和抗OX40L抗体可完全阻断CT诱导的Th2细胞因子反应。我们发现口服CT可诱导MLN中DC的选择性迁移、成熟和T细胞启动活性。Th2偏斜是由OX40L介导的，我们推测该分子可能是食物过敏原致敏的重要诱因。
Mice can be sensitized to food proteins by oral administration with the adjuvant cholera toxin (CT), such that they undergo anaphylaxis when rechallenged with the sensitizing allergen. In contrast, feeding of Ags alone leads to oral tolerance. Our aim was to define the mechanisms by which gastrointestinal dendritic cells (DCs) participate in the deviation of tolerance to allergic sensitization in the gut in response to CT. BALB/c mice were fed with CT or PBS. The impact of CT on DC subsets in the mesenteric lymph node (MLN) was assessed by flow cytometry. Ag presentation assays were performed with DCs isolated from the MLN of PBS- or CT-fed mice, using OVA-specific CD4(+) T cells as responder cells. Gene expression in MLN DCs was determined by real-time PCR, and neutralizing Abs were used to test the function of OX40 ligand (OX40L) in Th2 skewing. Oral administration of CT induced an increase in the total CD11c(+) population in the MLN. CT induced a selective increase in migration of the CD11c(+)CD11b(-)CD8 alpha(-) DC subset and the maturation of all DC subsets. Maturation of DCs in vivo enhanced T cell proliferation and cytokine secretion. Oral CT induced up-regulation of Jagged-2 and OX40L by MLN DCs. Neutralizing anti-OX40L Abs completely abrogated the CT-induced Th2 cytokine response. We show that oral CT induces selective DC migration, maturation, and T cell priming activity in the MLN. Th2 skewing is mediated by OX40L, and we speculate that this molecule may be an important inducer of allergic sensitization to food allergens.