Zhu Yaqiong, Liu Yuehui, Zhu Xinhua, Wang Zhi, Wang Meiqun
Department of Otorhinolaryngology Head and Neck Surgery, Second Affiliated Hospital of Nanchang University, Jiangxi, China.
Department of Otorhinolaryngology Head and Neck Surgery, Second Affiliated Hospital of Nanchang University, Jiangxi, China.
Eur J Pharmacol. 2020 Nov 15;887:173564. doi: 10.1016/j.ejphar.2020.173564. Epub 2020 Sep 15.
Group 2 innate lymphoid cells (ILC2s) and Th2 type immune response are critically involved in the pathogenesis of allergic rhinitis (AR), and this pathological process is influenced by microRNAs-mediated post-transcriptional regulation. The present study investigated the adaptation and function of miR-155 in AR patients and mouse model. We found that significantly increased miR-155 expression (1.63 ± 0.12 vs. 0.92 ± 0.11 in human, and 1.68 ± 0.15 vs. 1.06 ± 0.06 in mice) and ILC2s activity in nasal mucosa and serum in AR patients and mice. Administration of miR-155 antagomir significantly reduced the activity of ILC2s in nasal mucosa, suppressed the production of Th2 cytokines in serum and nasal mucosa, and alleviated the airway inflammation and allergic symptoms in AR mice, while miR-155 agomir increased ILC2s activity and production of Th2 cytokines and induced airway inflammation and allergic symptoms in control mice. Meanwhile, the expression of transcriptional factor c-Maf (0.57 ± 0.05 vs. 0.37 ± 0.04) in nasal mucosa in AR mice, which was significantly recovered by miR-155 antagomir (0.56 ± 0.04). Treatment with miR-155 agomir decreased c-Maf expression in nasal mucosa in control mice. This synchronized with the similar pattern in the current observations that miR-155 regulated Th2 cytokine (IL-4, IL-5, IL-9 and IL-13) production, airway inflammation and allergic symptoms in AR mice. Together, upregulation miR-155 suppressed the expression of transcriptional factor c-Maf and was critically involved in the ILC2s activation, which contributed to the airway inflammation and allergic symptoms in AR.
2型固有淋巴细胞（ILC2s）和Th2型免疫反应在变应性鼻炎（AR）的发病机制中起关键作用，且这一病理过程受微小RNA介导的转录后调控影响。本研究调查了miR-155在AR患者和小鼠模型中的适应性及功能。我们发现，AR患者和小鼠鼻黏膜及血清中miR-155表达显著增加（人类：1.63±0.12 vs. 0.92±0.11；小鼠：1.68±0.15 vs. 1.06±0.06）以及ILC2s活性增强。给予miR-155拮抗剂显著降低了鼻黏膜中ILC2s的活性，抑制了血清和鼻黏膜中Th2细胞因子的产生，并减轻了AR小鼠的气道炎症和过敏症状，而miR-155激动剂增加了ILC2s活性和Th2细胞因子的产生，并在对照小鼠中诱发了气道炎症和过敏症状。同时，AR小鼠鼻黏膜中转录因子c-Maf的表达（0.57±0.05 vs. 0.37±0.04），经miR-155拮抗剂处理后显著恢复（0.56±0.04）。用miR-155激动剂处理可降低对照小鼠鼻黏膜中c-Maf的表达。这与当前观察结果的相似模式一致，即miR-155调节AR小鼠中Th2细胞因子（IL-4、IL-5、IL-9和IL-13）的产生、气道炎症和过敏症状。总之，miR-155的上调抑制了转录因子c-Maf的表达，并在ILC2s激活中起关键作用，这导致了AR中的气道炎症和过敏症状。
