IgG4相关硬化性胆管炎（IgG4-SC）是以胆管周围大量IgG4阳性浆细胞浸润为特征的自身免疫性肝病，发病机制中以Th2细胞的免疫反应占主导。髓系源性抑制细胞（MDSCs）在肝内微环境中具有重要免疫调控作用，但尚未见其在该疾病中的相关研究。我们前期在IgG4-SC患者中观察到肝组织内B细胞（尤其是浆母细胞）表达活化NF-κB受体配体（RANKL）以及MDSCs表达RANK的有趣现象，拟通过针对RANKL/RANK/NF-κB途径刺激诱导MDSCs扩增等体内外实验回答下列科学问题：①RANKL和MDSCs是否与IgG4-SC的严重程度、临床预后相关？②MDSCs是如何参与调节Th细胞的分化与分泌功能，从而影响肝内Th1-Th2平衡，与B细胞/浆母细胞共同参与疾病的进展？本课题旨在通过研究IgG4-SC 时RANKL调控MDSCs的生物学行为机制，为探索更有效的免疫治疗策略提供理论依据。

Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is an autoimmune liver disease characterized by IgG4-positive lymphoplasmacytic infiltration of bile ducts and that causes biliary strictures. Th2 cells are implicated in the disease pathogenesis. Myeloid-derived suppressor cells (MDSCs) play vital roles in the hepatic immune microenvironment, but we have not yet seen MDSCs and IgG4-SC related research published. In our present studies, we investigated the dramatic increase of receptor activator of nuclear factor-κB ligand (RANKL) expression in IgG4-SC, which was mainly produced by B cells (especially plasmablast cells) in the liver. Then, we found that MDSCs, especially monocytic MDSCs expressed RANKL receptor RANK. We will utilize a series of in vivo and vitro experiments, such as the expansion of RANKL stimulated MDSCs through RANKL/RANK/NF-κB pathway, in order to answer the following scientific questions: ①What is the correlation between RANKL levels and the number of MDSCs with the severity of IgG4-SC and the clinical outcome? ②How do MDSCs regulate the differentiation and secretion of helper T cells in the intrahepatic microenvironment, thereby affecting the balance of Th1-Th2 and B cells/plasmablast, participating in the progression of the disease? Our study may elucidate the role of myeloid-derived suppressor cells in the pathogenesis of IgG4-related sclerosing cholangitis, and explore the promising immunotherapy strategy.