Abstract:
Type 2 innate lymphoid cells (ILC2s) exert an increasingly important influence on the pathological process of allergic rhinitis (AR), which is affected by microRNAs-mediated post-transcriptional regulation. This study aims to investigate the function of miR-150-5p in AR patients and the mouse model of AR. The mouse model of AR was established using the OVA challenge. The expressions of miR-150-5p, ICAM-1, p-p38 and p-GATA-3 were evaluated via RT-qPCR and western blot analysis. The level of ILC2s was examined with flow cytometry. Concentrations of OVA-specific IgE, IL-13 and IL-5 in serum were evaluated using ELISA. Histopathological examination was conducted through H&E staining. The interplay between ICAM-1 and miR-150-5p was determined through the DLR assay. The decreased miR-150-5p expression and increased ICAM-1, p-p38 and p-GATA-3 expressions and ILC2s levels were detected in AR patients and AR mice compared with controls. Treatment with miR-150-5p lentivirus alleviated AR symptoms (sneezing, rubbing, mucosa inflammation, serum type 2 cytokines and OVA-specific IgE) and lowered the ILC2s level in AR mice. MiR-150-5p was found to directly bind to 3\'-UTR of ICAM-1 and downregulate ICAM-1 expression, thereby descending the level of p-p38, p-GATA-3 and suppressing ILC2s function to alleviate AR symptoms. Treatment with Lenti-ICAM-1 counteracted these protective effects of miR-150-5p. Upregulation of miR-150-5p repressed the ICAM-1/p38 axis which was vital to ILC2s development and function, thereby alleviating allergic symptoms of AR.
摘要:
2型固有淋巴细胞(ILC2s)在变应性鼻炎(AR)的病理过程中发挥着越来越重要的作用,受microRNAs介导的转录后调控的影响。本研究旨在探讨miR-150-5p在AR患者和AR小鼠模型中的功能。使用OVA攻击建立AR的小鼠模型。miR-150-5p的表达,通过RT-qPCR和蛋白质印迹分析评估ICAM-1、p-p38和p-GATA-3。用流式细胞术检测ILC2s的水平。OVA特异性IgE的浓度,使用ELISA评估血清中的IL-13和IL-5。通过H&E染色进行组织病理学检查。通过DLR测定确定ICAM-1和miR-150-5p之间的相互作用。与对照组相比,在AR患者和AR小鼠中检测到miR-150-5p表达降低,ICAM-1,p-p38和p-GATA-3表达和ILC2s水平升高。用miR-150-5p慢病毒治疗可缓解AR症状(打喷嚏,摩擦,粘膜炎症,血清2型细胞因子和OVA特异性IgE)并降低AR小鼠的ILC2s水平。发现MiR-150-5p直接结合ICAM-1的3'-UTR并下调ICAM-1表达,从而降低p-p38、p-GATA-3的水平并抑制ILC2s功能以减轻AR症状。用Lenti-ICAM-1治疗抵消了miR-150-5p的这些保护作用。miR-150-5p的上调抑制了ICAM-1/p38轴,这对ILC2s的发育和功能至关重要,从而减轻AR的过敏症状。