microRNA-155通过SOCS对变应性鼻炎Th细胞的调控作用

llergic rhinitis is an important ,clinically prevalent disease worldwide with increasing incidence year by year, which results in reducing the quality of life and increasing the healthcare expenditures.But the exact pathogenic mechanisms are still not clear. Allergic rhinitis is a Th2-dominated inflammatory disease,and also includes Th17 inflammation type, which indicates the differentiation and development of Th cells are the critical point in the pathogenesis of allergic rhinitis.Recent research showed that miR-155 is the core critical miRNA related to the pathogenesis of allergic disease.It modulates the differentiation and function of Treg and Th17,but the underlying mechanisms are unclear.Multiple levels including nasal membrane tissue,peripherial blood mononuclear cells and anima lmodels , immunology and molecular biology in our research will be utilized to elucidate the modulation of miR-155 in the differentiation of Th cells and wheather it regulates the differentiation of Treg and Th17 by targeting SOCS.This will provide a new biomarker for the diagnosis and treatment of allergic rhinitis. This study has important scientific significance and potential application value.

变应性鼻炎是一种全球范围内临床上普遍的重要疾病，发病率逐年上升，影响患者的生活质量、导致医疗费用的增加，但是其确切的发病机制还不十分清楚。变应性鼻炎是一种主要以Th2炎症反应为主的变应性炎症，同时还具有Th17 炎症反应类型，可见Th细胞的极化发展是变应性鼻炎发病机制的核心。MiR-155是最近研究中发现与变应性炎症发病相关的核心miRNA，对于Treg 和Th17分化和功能有调控作用，但其确切的机制还不清楚。本课题通过患者组织、外周血单核细胞培养和动物模型体内实验，采用免疫学和分子生物学等手段，探讨miR-155在变应性鼻炎发病中对Th细胞分化的调控作用，及其是否通过关键靶基因SOCS调控Treg和Th17的分化，为变应性鼻炎的诊断和治疗提供新的生物学指标，具有重要的科学意义和潜在的应用价值。

目的：SOCS1（supressor of cytokine signaling，细胞因子信号抑制因子）和SOCS3在变应性鼻炎发病机制中对Th细胞分化发挥重要的调节作用。本研究的目的是检测SOCS1与SOCS3在变应性鼻炎中的表达情况并找到相对应的调控microRNAs,为变应性鼻炎的治疗提供一定的研究基础。.方法：通过采用实时定量PCR、免疫组织化学检测、western blot检测了SOCS1与SOCS3在变应性鼻炎外周血及组织中的表达情况。采用实时定量PCR检测相关调控microRNAs的表达，荧光素酶实验及变应性鼻炎动物试验被用来确定以SOCS3为靶基因的相关miroRNA及其对Th细胞因子的调控作用。.结果：SOCS1和SOCS3mRNA在变应性鼻炎患者外周血及鼻黏膜中的表达与正常对照组织相比较呈表达上调。SOCS3蛋白的表达在变应性鼻炎鼻黏膜组织中的表达显著增加。免疫组织化学检测显示SOCS3在变应性鼻炎和对照组织中相似地表达于表面上皮细胞、黏膜下腺体和血管内皮细胞。但是SOCS3在变应性鼻炎中特异性地表达于大量的炎性细胞，如嗜酸性粒细胞、单核细胞和淋巴细胞。.结论：在变应性鼻炎中mir30a-5p以SOCS3为靶基因在其发病机制中发挥重要的作用，mir124-3p上调Th2细胞因子及SOCS3的表达,这为变应性鼻炎的治疗提供了新的治疗策略。