Increased miR-124-3p alleviates type 2 inflammatory response in allergic rhinitis via IL-4Rα.
Increased miR-124-3p alleviates type 2 inflammatory response in allergic rhinitis via IL-4Rα.
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miR-124-3p 增加通过 IL-4Rα 减轻过敏性鼻炎的 2 型炎症反应
DOI：
10.1007/s00011-022-01614-x
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发表时间：
2022-11
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miRNAs在调节免疫应答中起着至关重要的作用。然而，miR-124- 3 p对过敏性鼻炎（AR）中2型炎症的影响尚不清楚。我们的目的是研究miR-124- 3 p在AR中的免疫调节作用及其机制。通过双荧光素酶报告基因测定证实了miR-124- 3 p和IL-4 R α之间的直接相互作用。培养来自小鼠的体外脾淋巴细胞和来自健康个体的外周血单核细胞（PBMC）并用miR-124- 3 p模拟物/抑制剂处理。将24只雌性C57 BL/C小鼠分为四组：对照组、AR模型组、miR-124- 3 p阿戈米尔组和miR-124- 3 p阿戈米尔组（每组n = 6）。根据喷嚏和鼻搔抓次数、血清HDM特异性IgE（sIgE）水平和鼻粘膜嗜酸性粒细胞浸润程度评价过敏反应。采用qPCR、免疫印迹、流式细胞术、免疫组织化学和免疫荧光法检测淋巴细胞或鼻粘膜中IL-4 R α、p-STAT 6和2型炎性细胞因子（IL-4、IL-5和IL-13）的表达。miR-124- 3 p直接靶向IL-4 R α的3 'UTR。miR-124- 3 p模拟物在体外降低小鼠脾淋巴细胞和人PBMC中的IL-4 R α、p-STAT 6、IL-4、IL-5和IL-13表达水平，而miR-124- 3 p抑制剂挽救了这些变化。此外，miR-124- 3 p agomir降低了鼻粘膜中IL-4 R α和IL-4的水平、脾脏中Th 2分化以及AR小鼠的过敏反应。此外，miR-124- 3 p拮抗剂可增加IL-4 R α和IL-4水平，进一步加重过敏反应。miR-124- 3 p可能通过调节IL-4 R α信号通路减轻AR中的2型炎症，miR-124- 3 p可能成为AR治疗的新靶点。在线版本包含补充材料，可通过10.1007/s 00011 -022-01614-x获取。
miRNAs play a crucial role in regulating immune responses. However, the effect of miR-124-3p on type 2 inflammation in allergic rhinitis (AR) is unclear. We aimed to study the immune regulation of miR-124-3p in AR and the mechanisms involved. The direct interaction between miR-124-3p and IL-4Rα was confirmed through a dual-luciferase reporter assay. In vitro splenic lymphocytes from mice and peripheral blood mononuclear cells (PBMCs) from healthy individuals were cultured and treated with miR-124-3p mimic/inhibitor. Twenty-four female C57BL/C mice were divided into four groups: control, AR model, miR-124-3p agomir, and miR-124-3p antagomir groups (n = 6 per group). The allergic responses were evaluated based on the number of sneezing and nasal scratching, the serum HDM-specific IgE (sIgE) levels, and the degree of nasal mucosa eosinophil infiltration. The expression of IL-4Rα, p-STAT6, and type 2 inflammatory cytokines (IL-4, IL-5 and IL-13) in lymphocytes or nasal mucosa was determined by qPCR, western blotting, flow cytometry, immunohistochemistry and immunofluorescence. miR-124-3p directly targets the 3'UTR of IL-4Rα. The miR-124-3p mimic lowered the IL-4Rα, p-STAT6, IL-4, IL-5, and IL-13 expression levels in both mouse splenic lymphocytes and human PBMCs in vitro, and the miR-124-3p inhibitor rescued these changes. Furthermore, the miR-124-3p agomir decreased the levels of IL-4Rα and IL-4 in nasal mucosa, Th2 differentiation in spleen, and allergic response in AR mice. Moreover, the miR-124-3p antagonist increased the IL-4Rα and IL-4 levels and further aggravated the allergic responses. miR-124-3p might attenuate type 2 inflammation in AR by regulating IL-4Rα signaling, and miR-124-3p may be a promising new target in AR treatment. The online version contains supplementary material available at 10.1007/s00011-022-01614-x.