Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, 238 Jie-Fang Road, Wuhan, Hubei 430060, PR China.
Department of Otolaryngology-Head and Neck Surgery, General Hospital of The Central Theater Command of The People's Liberation Army, Wuhan 430070, Hubei, PR China.
Life Sci. 2021 Nov 1;284:119922. doi: 10.1016/j.lfs.2021.119922. Epub 2021 Sep 1.
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 (P < 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 (P < 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 (P < 0.05).
Notch2 promotes the differentiation of Treg cells by upregulating FOXP3 expression, thus significantly inhibiting the inflammatory response of AR.
Notch 信号与多种疾病密切相关，但 Notch2 在过敏性鼻炎（AR）中的作用尚不清楚。本研究旨在探讨 Notch2 对 Treg 细胞分化及 AR 炎症反应的影响。
收集外周血（包括 101 例 AR 患者和 66 例对照）和鼻黏膜（包括 19 例 AR 患者和 17 例对照），检测 Notch2、NICD2 和 FOXP3 的表达水平。选择人源 CD4+T 细胞，检测 Notch2 对 Treg 细胞分化和 FOXP3 的影响。建立 AR 小鼠模型，给予过表达 Notch2 的慢病毒。然后评估过敏症状、OVA-sIgE 滴度、鼻黏膜炎症、Th1/Th2/Th17 细胞因子和脾 Treg 细胞。
与对照组相比，AR 组 Notch2 的表达降低，且 Notch2 的表达与过敏程度呈负相关（P<0.01）。AR 患者鼻黏膜 Notch2、NICD2 和 FOXP3 的表达水平降低。Notch2 可促进体外人 Treg 细胞的分化（P<0.05），并可直接促进 FOXP3 转录。动物实验表明，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（P<0.05）。
Notch2 通过上调 FOXP3 表达促进 Treg 细胞分化，从而显著抑制 AR 的炎症反应。
