Imperatorin exerts antiallergic effects in Th2-mediated allergic asthma via induction of IL-10-producing regulatory T cells by modulating the function of dendritic cells
Imperatorin exerts antiallergic effects in Th2-mediated allergic asthma via induction of IL-10-producing regulatory T cells by modulating the function of dendritic cells
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欧前胡素通过调节树突状细胞功能诱导产生IL-10的调节性T细胞在Th2介导的过敏性哮喘中发挥抗过敏作用
DOI：
10.1016/j.phrs.2016.04.030
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发表时间：
2016-08-01
影响因子：
9.3
通讯作者：
Lee, Yueh-Lun
中科院分区：
文献类型：
--
作者：
Lin, Chu-Lun;Hsiao, George;Lee, Yueh-Lun
香豆素是一种呋喃香豆素类化合物，广泛存在于多种中草药中，具有多种生物活性。为此，我们研究了欧前胡素对哮喘小鼠的抗过敏作用，并探讨了欧前胡素对免疫细胞的免疫调节作用。我们使用卵白蛋白(OVA)诱导的哮喘小鼠模型来评估欧前胡素的治疗潜力。此外，骨髓来源的树突状细胞(DC；BMDCs)被用来阐明欧前胡素是否通过改变DC调节T细胞的能力而发挥抗过敏作用。口服欧前胡素可降低OVA致敏和激发小鼠血清中OVA特异性免疫球蛋白E(IgE)的产生，减轻气道高反应性(AHR)，并以剂量依赖的方式减轻气道炎症。值得注意的是，在欧前胡素治疗的小鼠中，Th2细胞因子和趋化因子的分泌减少，产生白细胞介素10的调节性T细胞(Tregs)的数量增加。欧前胡素抑制脂多糖刺激的BMDCs产生促炎细胞因子和IL-12，但促进IL-10的分泌。与完全成熟的DC相比，欧前胡素处理的DC在体外表达高水平的可诱导共刺激配体(ICOSL)和Jaggedl分子，并具有促进产生IL-10的CD4(+)T细胞的调节能力。此外，欧前胡素直接抑制活化的CD4(+)T细胞的增殖和细胞因子的产生。欧前胡素可能不仅通过刺激树突状细胞的诱导，还可能通过直接抑制Th2细胞的激活而具有治疗Th2介导的过敏性哮喘的潜力。这些发现为欧前胡素如何影响Th2免疫反应以及欧前胡素作为Treg类免疫调节剂治疗过敏性哮喘的发展提供了新的见解。(C)2016爱思唯尔有限公司。保留所有权利。
Imperatorin is a furanocoumarin compound which exists in many medicinal herbs and possesses various biological activities. Herein, we investigated the antiallergic effects of imperatorin in asthmatic mice and explored the immunomodulatory actions of imperatorin on immune cells. We used a murine model of ovalbumin (OVA)-induced asthma to evaluate the therapeutic potential of imperatorin. Additionally, bone marrow-derived dendritic cells (DCs; BMDCs) were used to clarify whether imperatorin exerts an antiallergic effect through altering the ability of DCs to regulate T cells. Oral administration of imperatorin to OVA-sensitized and challenged mice decreased serum OVA-specific immunoglobulin E (IgE) production, attenuated the airway hyperresponsiveness (AHR), and alleviated airway inflammation in a dose-dependent manner. Notably, secretions of Th2 cytokines and chemokines were reduced, and numbers of interleukin (IL)-10-producing regulatory T cells (Tregs) increased in imperatorin-treated mice. Imperatorin inhibited proinflammatory cytokines and IL-12 production but enhanced IL-10 secretion by lipopolysaccharide (LPS)-stimulated BMDCs. Compared to fully mature DCs, imperatorin-treated DCs expressed high levels of the inducible costimulatory ligand (ICOSL) and Jaggedl molecules, and had the regulatory capacity to promote the generation of IL-10-producing CD4(+) T cells in vitro. Additionally, imperatorin directly suppressed activated CD4(+) T-cell proliferation and cytokine production. Imperatorin may possess therapeutic potential against Th2-mediated allergic asthma not only via stimulating DC induction of Tregs but also via direct inhibition of Th2 cell activation. These findings provide new insights into how imperatorin affects the Th2 immune response and the development of imperatorin as a Treg-type immunomodulatory agent to treat allergic asthma. (C) 2016 Elsevier Ltd. All rights reserved.