Interferon-λ Mediates Oral Tolerance and Inhibits Antigen-Specific, T-Helper 2 Cell-Mediated Inflammation in Mouse Intestine
Interferon-λ Mediates Oral Tolerance and Inhibits Antigen-Specific, T-Helper 2 Cell-Mediated Inflammation in Mouse Intestine
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DOI：
10.1053/j.gastro.2011.04.006
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发表时间：
2011-07-01
期刊：
影响因子：
29.4
通讯作者：
Yang, Ping-Chang
中科院分区：
文献类型：
--
作者：
He, Shao-Heng;Chen, Xiao;Yang, Ping-Chang
背景与目的：口服耐受是胃肠道内环境稳定的重要组成部分，但其发展机制尚未完全了解。口服耐受性的丧失发生在胃肠道中食物过敏原相关的炎症期间。干扰素（IFN）-λ调节免疫，但其在口服耐受中的作用尚不清楚。我们研究了IFN-λ在口服耐受性发展中的作用和机制及其对抗原诱导的T辅助细胞（Th）-2介导的肠道炎症的影响。方法：采用免疫组化、流式细胞术或免疫印迹分析法分析IFN-λ及其受体的表达。致耐受性树突状细胞（DC）和调节性T细胞在体外和体内进行了检查。使用抗原诱导的Th 2细胞介导的肠道炎症的小鼠模型来检查IFN-λ和T细胞在肠道中口服耐受性中的作用。结果：CD 3（+）细胞表达IFN-λ受体，其在抗原特异性或非特异性激活后上调。IFN-λ与其受体之间的相互作用诱导T细胞凋亡及其随后被DC吞噬。这导致在体外和体内产生致耐受性DC和调节性T细胞。被动转移IFN-λ致敏的CD 3（+）细胞可抑制Th 2细胞介导的肠道炎症。结论：IFN-λ参与小鼠肠道中口服耐受性的发展和维持;它可能用于抑制患者中抗原特异性Th 2细胞介导的炎症。
BACKGROUND & AIMS: Oral tolerance is an important component of gastrointestinal homeostasis, but mechanisms of its development are not fully understood. Loss of oral tolerance occurs during food allergen-related inflammation in the gastrointestinal tract. Interferon (IFN)-lambda regulates immunity, but its role in oral tolerance is not clear. We investigated the role and the mechanism of IFN-lambda in the development of oral tolerance and its effect on antigen-induced, T-helper (Th)-2 cell-mediated inflammation in the intestine. METHODS: Expression of IFN-lambda and its receptor were analyzed by immunohistochemical, flow cytometric, or immunoblot analyses. Tolerogenic dendritic cells (DCs) and regulatory T cells were examined in vitro and in vivo. A mouse model of antigen-induced, Th2 cell-mediated intestinal inflammation was used to examine the role of IFN-lambda and T cells in oral tolerance in the intestine. RESULTS: CD3(+) cells expressed the IFN-lambda receptor, which was up-regulated following antigen-specific or nonspecific activation. Interaction between IFN-lambda and its receptor induced apoptosis of T cells and their subsequent phagocytosis by DCs. This led to the generation of tolerogenic DCs and T regulatory cells in vitro and in vivo. Passive transfer of IFN-lambda-primed CD3(+) cells inhibited Th2 cell-mediated inflammation in the intestine. CONCLUSIONS: IFN-lambda is involved in development and maintenance of oral tolerance in the intestines of mice; it might be used to suppress antigen-specific Th2 cell-mediated inflammation in patients.