miR-19a调控SOX4参与过敏性鼻炎CD4+T细胞分化的作用及机制

Allergic rhinitis (AR) is a kind of harmful disease for human being. The abnormal differentiation of CD4+T cells and Th1/Th2 imbalance are key pathologic features of AR, but the molecular mechanisms are unclear. We previously found miR-19a was one of high-ranked upregulated miRNAs in AR patients by miRNA-seq. SOX4, are an important negative regulator of T cell differentiation, was indentified as a direct target of miR-19a. We speculate: Overexpression of miR-19a resulted in decreased SOX4 levels accompanied by an increased CD4+T cells differentiation and Th1/Th2 imbalance. In the present study, we will investigate the influnce of miR-19a on CD4+T cells differentiation induced by superantigen and allergens in vitro and in vivo and Th1/Th2 cytokines levels by over- and down-expression of miR-19a in cell culture.

过敏性鼻炎（allergic rhinitis, AR）是严重危害人类健康的疾病，发病的核心特征之一是CD4+T淋巴细胞分化异常及Th1/Th2细胞免疫失衡，其确切的调控机制尚未完全阐明。我们通过深度测序（miRNA-seq）发现：AR患者外周血单个核细胞（PBMC）miR-19a的表达较正常对照明显上调。SOX4 3’UTR区域存在miR-19a的保守结合位点，可负向调控T细胞分化。我们推测“miR-19a的上调导致其靶基因SOX4的下调，影响CD4+T细胞活化，打破Th1/Th2细胞免疫平衡，从而参与了AR的发生”。为证实该假说，我将观察miR-19a在体内、体外变应原刺激的CD4+T细胞分化过程中的表达情况及其对Th1/Th2细胞因子的影响及分子机制。本研究将进一步揭示AR的发病机制，为其有效防治提供新思路和新的分子靶点。

过敏性鼻炎（allergic rhinitis, AR）是严重危害人类健康的疾病，发病的核心特征之一是CD4+T淋巴细胞分化异常及Th1/Th2细胞免疫失衡，其确切的调控机制尚未完全阐明。前期通过深度测序（miRNA-seq）发现：AR患者外周血单个核细胞（PBMC）miR-19a的表达较正常对照明显上调。SOX4 3’UTR区域存在miR-19a的保守结合位点，可负向调控Th2细胞分化。研究募集了50例尘螨AR患者与50例正常对照受试者。研究结果发现：过敏性鼻炎患者较正常对照受试者外周血单个核细胞中miR-19a表达显著增高，SOX4基因表达显著降低, IL13基因表达显著增高，IL13表达与miR-19a表达呈正相关性。流式细胞术分选外周血免疫细胞亚群，结果显示miR-19a主要在PBMC中的T细胞亚群表达，且AR患者miR-19a在外周血T细胞亚群中表达较正常对照组增高；miR-19a在Th细胞的分化与活化过程中表达逐渐增加，T细胞特异性刺激剂及超抗原可诱导miR-19a表达上调。过表达miR-19a可有效降低SOX4基因及蛋白的表达。本研究有助于更深入地阐明过敏性鼻炎炎症发生的发病机理，从应用前景方面可能为设计过敏性鼻炎的治疗提供新的分子靶标。