Notch signaling is closely related to a variety of diseases, but the role of Notch2 in allergic rhinitis (AR) remain unclear. This study was performed to investigate the effects of Notch2 on the differentiation of Treg cells and on the inflammatory response of AR. Peripheral blood (including 101 AR patients and 66 Controls) and nasal mucosa (including 19 AR patients and 17 Controls) were collected to detect the expression levels of Notch2, NICD2 and FOXP3. CD4+ T cells of human origin were selected to detect the effects of Notch2 on the differentiation of Treg cells and FOXP3. An AR mouse model was established, and lentiviruses overexpressing Notch2 were administered. Then, allergic symptoms, OVA-sIgE titers, nasal mucosal inflammation, Th1/Th2/Th17 cytokines and splenic Treg cells were assessed. Compared with that in the Control group, the expression of Notch2 in the AR group was decreased, and Notch2 expression was negatively correlated with the degree of allergy ( < 0.01). The expression levels of Notch2, NICD2 and FOXP3 were decreased in the nasal mucosa of AR patients. Notch2 can promote the differentiation of human Treg cells in vitro ( < 0.05), and Notch2 can directly promote FOXP3 transcription. Animal experiments showed after the upregulation of Notch2 expression, the allergic inflammatory of mice with AR was reduced, the differentiation of Treg cells was increased, and the imbalance of T cells was reversed ( < 0.05). Notch2 promotes the differentiation of Treg cells by upregulating FOXP3 expression, thus significantly inhibiting the inflammatory response of AR.

中文翻译：

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Notch2通过促进FOXP3表达和Treg细胞分化抑制过敏性鼻炎的发展


Notch信号与多种疾病密切相关，但Notch2在过敏性鼻炎（AR）中的作用仍不清楚。本研究旨在探讨Notch2对Treg细胞分化和AR炎症反应的影响。采集外周血(包括101例AR患者和66例对照者)和鼻粘膜(包括19例AR患者和17例对照者)检测Notch2、NICD2和FOXP3的表达水平。选择人源CD4+ T细胞检测Notch2对Treg细胞和FOXP3分化的影响。建立AR小鼠模型，并给予过表达Notch2的慢病毒。然后评估过敏症状、OVA-sIgE滴度、鼻粘膜炎症、Th1/Th2/Th17细胞因子和脾Treg细胞。与Control组相比，AR组Notch2表达量降低，且Notch2表达量与过敏程度呈负相关（<0.01）。 AR患者鼻粘膜中Notch2、NICD2和FOXP3的表达水平降低。 Notch2可以在体外促进人Treg细胞的分化（<0.05），并且Notch2可以直接促进FOXP3转录。动物实验显示，上调Notch2表达后，AR小鼠的过敏炎症减轻，Treg细胞分化增加，T细胞失衡得到逆转（<0.05）。 Notch2通过上调FOXP3表达促进Treg细胞分化，从而显着抑制AR的炎症反应。