IgG4相关性疾病（IgG4-RD）是新认识的一种以血清IgG4升高、受累器官炎症、硬化，伴大量IgG4阳性浆细胞浸润的疾病。我们前期研究发现IgG4-RD患者外周血中B细胞亚类表达、功能以及免疫球蛋白类别转换异常，导致分泌IgG4的浆母细胞显著升高。本课题将在上述基础上进一步探讨微小核糖体 RNA（miRNA）对IgG4-RD患者B细胞功能的调控。预实验发现，与干燥综合征和健康对照相比，IgG4-RD患者异常表达的miRNA富集于PI3K-AKT-mTOR信号通路。因此我们将验证并确定1-2种差异表达的miRNA，在外周血和组织中B细胞进行相应的敲减及过表达，确证其调节B细胞中PI3K-AKT-mTOR信号通路和B细胞功能的作用；最后，利用IgG4-RD实验鼠模型，体内证实相应的miRNA对PI3K-AKT-mTOR信号通路活化的调控，以及对B细胞活化、分化和疾病表型的影响。

IgG4 related disease (IgG4-RD) is a newly recognized fibro-inflammatory disease, which is characterized by elevated serum IgG4, swelling and fibrosis of affected organs, accompanied by massive lymphocytes and IgG4 positive plasma cells infiltration of involved organs/tissues. Our previous study revealed that the phenotype and function of peripheral blood B cell subsets were abnormal, as well as the abnormality of immunoglobulin class switch, resulting in large amounts of IgG4 secreting plasmablasts. Our present study is to further investigate the mechanism of B cells activation regulated by microRNA (miRNA) in IgG4-RD. From our previous study, we found the differentially expressed miRNAs were enriched in PI3K-AKT-mTOR signaling pathway compared with Sjogren syndrome and health control. So we will testify 1-2 differentially expressed miRNA in peripheral blood B cells and tissue B cells, and then by knocking down or overexpression of selected miRNA in B cells in vitro, we aim to observe the changes of PI3K-AKT-mTOR signaling pathway activation and B cell phenotype and function. We then will further verify in vivo how the selected miRNA regulating the activation of the PI3K-AKT-mTOR signaling pathway, the mouse model disease phenotype and B cell phenotype and function.