Dietary Flavonoid Naringenin Induces Regulatory T Cells via an Aryl Hydrocarbon Receptor Mediated Pathway
Dietary Flavonoid Naringenin Induces Regulatory T Cells via an Aryl Hydrocarbon Receptor Mediated Pathway
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DOI：
10.1021/jf204625y
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发表时间：
2012-03-07
影响因子：
6.1
通讯作者：
Totsuka, Mamoru
中科院分区：
文献类型：
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作者：
Wang, Hsi-Kai;Yeh, Chen-Hao;Totsuka, Mamoru
芳烃受体(AhR)是一种介导异物解毒的转录因子，在调节性T细胞(Treg)的诱导中发挥着重要作用。Treg调节免疫系统，从而抑制过敏和自身免疫性疾病。本研究旨在确定新型抗过敏饮食因子，重点是具有潜在AhR激动剂活性的黄酮类化合物。在用报告试验测试的25个膳食类黄酮样本中，8个样本显示显著诱导了AhR依赖的转录活性。随后的T细胞增殖抑制实验确定柚皮苷元是唯一能够刺激Treg诱导的样本；值得注意的是，这种诱导被AhR拮抗剂共同处理而被消除。事实上，无论是否存在转化生长因子-β，柚皮苷元都能诱导CD4(+)Foxp3(+)Tregs，这表明传统的依赖于转化生长因子-β的信号通路可能不参与其中。
The aryl hydrocarbon receptor (AhR), a transcription factor mediating xenobiotic detoxification, plays a considerable role in regulatory T cell (Treg) induction. Tregs regulate the immune system, thus suppressing allergies and autoimmune diseases. This study aims to identify new types of antiallergic dietary factors, with focus on the flavonoids with potential AhR agonistic activity. Among 25 dietary flavonoid samples tested using a reporter assay, 8 showed marked induction of AhR-dependent transcriptional activity. The subsequent T cell proliferation suppression assay identified naringenin as the only sample capable of stimulating Treg induction; notably, this induction was eliminated by cotreatment with AhR antagonists. Indeed, naringenin induced CD4(+)Foxp3(+) Tregs, irrespective of the presence of the transforming growth factor-beta (TGF-beta), indicating that the conventional TGF-beta-dependent signaling pathway might not be involved.