巨噬细胞（Mφ）极化异常参与类风湿关节炎（RA）进程，但其机制尚不明确。课题组前期发现人溶菌酶（Lysozyme，LYZ）在RA患者滑膜液显著高表达，可作为RA的新鉴别诊断分子标志物。单细胞测序发现LYZ在滑膜液Mφ中显著高表达，且实验证实LYZ促进M1型Mφ相关炎性因子IL-6的表达；促炎因子TNF-α或LPS可激活Mφ肝X受体（LXR）并上调LYZ，结合LXRα可结合到LYZ启动子现象，推测：促炎因子-LXRα-LYZ信号轴介导的Mφ极化异常在RA进程中具有重要作用。本项目采用体内、外Mφ敲除或过表达小鼠溶菌酶（Lyz1），结合小鼠RA模型、RNA-seq、Lyz1CoIP及Lyz1下游信号通路干预等方法，明确促炎因子-LXRα-LYZ信号轴对滑膜Mφ功能的影响及其在RA中作用机制。旨在深化LYZ在滑膜Mφ极化及RA进程中的作用及分子机制，为基于LYZ为靶点的RA干预策略提供实验依据。

The abnormal polarization of macrophages (Mφ) is involved in the process of rheumatoid arthritis (RA), with unknown mechanisms. Our previous pilot studies revealed that the protein level of human lysozyme (LYZ) was significantly increased in the synovial fluid of RA patients, which could be used as a new diagnosistic molecular marker for RA. Single-cell sequencing revealed that LYZ was significantly overexpressed in synovial fluid Mφ, and we further confirmed that LYZ promoted the expression of M1 Mφ-associated inflammatory factor, IL-6. We further found that the proinflammatory factors, TNF-α or LPS, can activate Mφ LXR as well as up-regulate LYZ. In combination with the findings that LXRα could directly bind to the promoter region of LYZ, we speculated that Mφ polarization abnormality mediated by the pro-inflammatory factors-LXRα-LYZ axis may have an important role in RA process. To this end, this project will use in vivo and in vitro Mφ knockout or overexpression of Mouse Lyz1 methods, together with mouse RA model, RNA-seq, Lyz1 CoIP, and Lyz1 downstream signal pathway intervention and other methods to verify the pro-inflammatory factor-LXRα-LYZ signal axis in regulating the function of synovial Mφ and its role in the pathogenesis of RA. The purpose of the current project is to deepen the role and molecular mechanism of LYZ in synovial Mφ polarization and RA process, and provide experimental basis for RA intervention strategies based on targeting LYZ.