Intestinal epithelial cells express galectin-9 in patients with food allergy that plays a critical role in sustaining allergic status in mouse intestine
Intestinal epithelial cells express galectin-9 in patients with food allergy that plays a critical role in sustaining allergic status in mouse intestine
复制标题
食物过敏患者的肠上皮细胞表达半乳糖凝集素 9，这在维持小鼠肠道过敏状态中发挥着关键作用
DOI：
10.1111/j.1398-9995.2011.02585.x
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发表时间：
2011-08-01
期刊：
影响因子：
12.4
通讯作者：
Yang, P. -C.
中科院分区：
文献类型：
--
作者：
Chen, X.;Song, C. -H.;Yang, P. -C.
背景和目的：维持体内过敏性超敏状态的机制尚不清楚。半乳糖凝集素9（Gal-9）具有很强的免疫调节能力。本研究旨在阐明 Gal-9 在维持肠道过敏状态中的作用。方法：对 20 名消化性溃疡和食物过敏 (FA) 患者进行十二指肠活检。从蛋白水平和mRNA水平检测肠组织中Gal-9的表达。建立了肠上皮细胞（IEC）与肥大细胞或树突状细胞（DC）与T细胞的两种共培养系统，以研究肠道中Gal-9的来源以及Gal-9调节DC表型和维持T辅助细胞2极化的机制。结果：正常IEC显示Gal-9轻度表达，而FA患者中Gal-9表达显着增强。肥大细胞能够通过释放激活 IEC 上蛋白酶激活受体 2 的类胰蛋白酶来诱导 IEC 产生 Gal-9。 Gal-9 通过激活环磷酸鸟苷 (cGMP) 途径将 TIM3 连接到 DC 上，从而激活 DC 产生 TIM4（T 细胞免疫球蛋白粘蛋白结构域）。在小鼠 FA 模型中，阻断 Gal-9 可以抑制肠道内的过敏性超敏状态和抗原特异性 Th2 反应。结论：IEC 衍生的 Gal-9 有助于维持肠道内的过敏状态。
Background and aims: Mechanisms in sustaining the allergic hypersensitivity status in the body are unclear. Galectin-9 (Gal-9) has strong immune regulatory capacity. The present study aims to elucidate the role of Gal-9 in sustaining allergic status in the intestine.Methods: Duodenal biopsies were obtained from 20 patients with peptic ulcer and food allergy (FA). The expression of Gal-9 in intestinal tissue was examined at both protein level and mRNA level. Two coculture systems with intestinal epithelial cells (IEC) and mast cells, or dendritic cells (DC) and T cells were established to investigate the source of Gal-9 in the intestine and the mechanism by which Gal-9 modulated DC's phenotyping and sustained the T helper 2 polarization.Results: Normal IEC showed mild expression of Gal-9 that was markedly enhanced in patients with FA. Mast cells had the capability to induce IEC to produce Gal-9 via releasing tryptase that activated the proteinase-activated receptor 2 on IEC. Gal-9 activated DC to produce TIM4 (T-cell immunoglobulin mucin domain) via ligating TIM3 on DC via activating the cyclic guanosine monophosphate (cGMP) pathway. In a mouse FA model, blocking Gal-9 inhibited the allergic hypersensitivity status and the antigen-specific Th2 response in the intestine.Conclusions: IEC-derived Gal-9 contributes to sustaining the allergic status in the intestine.