变应性鼻炎血浆细胞外囊泡通过miR-144-3p调控JAK1/3-STAT6信号通路介导Th2分化

变应性鼻炎(AR)患病率高，严重影响患者的生活质量，其发病与Th1/Th2免疫失衡密切相关，但具体的调控机制尚需进一步解析。细胞外囊泡(EV)包含miRNA等多种活性成份，可参与细胞通讯和免疫应答等过程。文献表明气道上皮细胞及树突状细胞等均可释放EV而介导呼吸道变应性炎症。不过AR患者体液中的EV更能反映疾病的真实状态，其对Th1/Th2免疫失衡的作用尚未知。我们预实验发现AR患者血浆EV可显著促进Th2细胞的分化，并且揭示了AR患者和健康人血浆EV中包含差异性表达的miRNA，进一步筛选出miR-144-3p作为调控Th2分化的候选miRNA，不过具体的分子机制还需进一步探讨。因此，本课题将深入地探讨AR-EV来源miR-144-3p对Th2分化的调控作用，并从JAK1/3-STAT6信号通路阐明具体分子机制。本研究将为AR的发病机制提供新的诠释，也为AR患者的临床治疗提供新的靶点。

Allergic rhinitis (AR) is a chronic upper airway inflammation that has very high prevalence rate and causes poor quality of life for AR patients. The development of AR is involved with the immune imbalance of Th1/Th2, but the detailed mechanisms remained to be further investigated. It’s been reported that extracellular vesicles (EVs) are nano-vesicles that contain abundant biological components such as RNAs, and are extensively involved with cellular communication and immune responses. Also, it’s been reported that epithelial cells and dendritic cells were able to release EVs that mediated the development of allergic airway inflammation. However, EVs in the body fluids of AR patients are better indicators of the state of the disease, but it still remains unclear in regards with the role of plasma EVs in the imbalance of Th1/Th2. We have successfully demonstrated that plasma EVs from patients with mild AR (M-AR-EVs) and moderate-severe AR (S-AR-EVs) significantly promote the differentiation of CD4+T cells to Th2 cells, characterized the differential miRNAs in HC-EVs and AR-EVs by miRNA sequencing, and identified that miR-144-3p as the potential candidate in the regulation of Th2 differentiation. However, the detailed mechanisms about the miR-144-3p-medieated Th2 differentiation remained to be further investigated. In our study, we will further explore the effects of miR-144-3p contained in AR-EVs in the differentiation of Th2 cells, and it’s effects on JAK1/3-STAT6 signaling pathway. In total, our study would provide novel mechanism for understanding of the pathogenesis of AR and strategies for the clinical therapy of AR patients.