肽精氨酸脱亚氨基酶Ⅳ（PADI4）是一个重要的基因转录共调节因子，通过对造血干细胞、肿瘤等多种细胞核内组蛋白及其相关蛋白的瓜氨酸化修饰，调控细胞的分化、增殖或凋亡。巨噬细胞（Mø）和成纤维样细胞（FLS）是RA滑膜（RA-ST）病变的两个关键效应细胞，均高表达PADI4。项目组前期已阐明PADI4能促进RA-FLS增殖、抑制凋亡并促进分泌炎症因子。本项目聚焦于RA-ST Mø，采用免疫组化技术阐明不同病程Mø极化模式及增殖状况，分析Mø内PADI4过表达促进M1/M2、破骨细胞/成骨细胞失平衡的作用;在细胞共培养体系中采用激光共聚焦动态分析Mø、FCM等研究M1、M2细胞与FLS间相互调控对Mø极化、增殖及分泌炎症因子的影响。构建shRNA-PADI4壳聚糖纳米靶向载体，在RA模型中探索分别或联合靶向抑制FLS、Mø、M1、破骨细胞表达PADI4的精准策略在RA防治中的作用。

The peptidylarginine deiminase IV (PADI4) is an important co-regulator of gene transcription, which converts arginine residues at histone tails and other associated protein to citrulline. Citrullination can take place at hematopoietic stem cells, tumor cells and other cell nucleus, regulation of cell differentiation, proliferation or apoptosis. Macrophages (Mø) and fibroblast-like cells (FLS) highly expressed PADI4 are two key effector cells in the RA synovium (RA-ST). Our previous study found that PADI4 promote RA-FLS proliferation, secretion of inflammatory cytokines and inhibition of apoptosis. This study will continue to explore the following research work: 1) Using immunohistochemistry and fluorescent antibody technique, to clarify M1/M2 Macrophages polarization mode in the different course of RA-SM. 2) To explore its role of PADI4 overexpressed in synovium Macrophages to promote M1 and M2, osteoclasts and osteoblasts disequilibrium. 3) In the cell co-culture system using a confocal laser dynamic analysis, flow cytometry technology to clarify that the interactions between M1, M2 Macrophages and FLS, and the effect on Macrophages polarization, proliferation and secretion of inflammatory cytokines. 4) Construction of shRNA-PADI4 nano-targeting vectors, at the level of RA models, to explore the precise role of therapeutic strategies, separately or combined with targeted inhibition of FLS, Mø, M1 and osteoclasts expression PADI4 in the prevention and treatment of RA.