Tangeretin promotes regulatory T cell differentiation by inhibiting Notch1/Jagged1 signaling in allergic rhinitis
Tangeretin promotes regulatory T cell differentiation by inhibiting Notch1/Jagged1 signaling in allergic rhinitis
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Tangeretin 通过抑制过敏性鼻炎中的 Notch1/Jagged1 信号传导促进调节性 T 细胞分化
DOI：
10.1016/j.intimp.2019.04.039
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发表时间：
2019-07-01
影响因子：
5.6
通讯作者：
Chen, Shi-Ming
中科院分区：
文献类型：
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作者：
Xu, Shan;Kong, Yong-Gang;Chen, Shi-Ming
背景与目的：柑橘素具有广泛的抗炎作用。本研究旨在评估橘子素是否具有调节调节T调节细胞（T细胞）和减轻变应性鼻炎（AR）的功能。建立卵清蛋白（OVA）诱导的AR动物模型，观察其过敏症状评分、OVA特异性IgE滴度、组织病理学特征和辅助性T细胞（Th细胞）的变化（Th 1、Th 2和Th 17）相关的细胞因子水平。检测Notch 1/Jagged 1和FOXP 3的表达水平，以及脾脏中T淋巴细胞的比例。结果：与AR组相比，给予橘子素和地塞米松均能减轻气道炎症，降低血清中OVA诱导的IgE的产生，但只有橘子素能恢复气道内细胞因子的平衡。在AR小鼠或幼稚CD 4 + T细胞分化中，脾CD 4 + CD 25 + F0 XP 3 + Treg细胞和转录因子F0 XP 3的丰度在橘子皮素处理下显著增加，随后伴随Notchl/Jaggedl表达的减少。结论：陈皮素可通过抑制Notch 1/Jagged 1的表达，促进调节性T细胞反应，进而促进FOXP 3/Treg细胞的分化，有望成为治疗AR的新药物。
Background and objective: Tangeretin demonstrates broad anti-inflammatory effects. The present study aimed to assess whether tangeretin functions in regulating T-regulatory cells (Tregs) and alleviating allergic rhinitis (AR).Methods: An ovalbumin (OVA)-induced AR animal model was constructed to monitor the changes in the allergic symptom score, OVA-specific IgE titers, histopathological characteristics and T-helper cell (Th1, Th2, and Th17)related cytokine levels under tangeretin or dexamethasone (DXM) administration. The expression levels of Notch1/Jagged1 and FOXP3, and the proportion of Tregs in the spleens of these animals, were also detected. Furthermore, purified naive CD4 + T cells were utilized to assess the effects of tangeretin on Notchl expression and their differentiation in vitro.Results: Both tangeretin and DXM administration alleviated airway inflammation, decreased the production of serum OVA-induced IgE, but only tangeretin administration restored the balance of cytokine profiles compared with those in the AR group. The abundance of splenic CD4 + CD25 + FOXP3 + Treg cells and the transcription factor FOXP3 were significantly increased under tangeretin treatment, either in AR mice or in naive CD4 + T-cell differentiation, followed by a concomitant reduction in Notchl/Jaggedl expression. However, as a positive control, the treatment of allergic rhinitis with dexamethasone was not related to the expression of Notch1/Jagged1 or the differentiation of Treg cells.Conclusion: Tangeretin could promote regulatory T cell responses by inhibiting Notch1/Jagged1 expression, followed by promoting FOXP3/Treg cell differentiation and thus could serve as a novel curative therapeutic for AR.