真菌性角膜炎是我国首位的感染性角膜病。DC-SIGN识别真菌参与机体免疫反应。本研究拟从动物模型及体外细胞培养分析角膜抗真菌免疫中模式识别受体DC-SIGN的作用。首先通过定性及定量实验研究DC-SIGN在真菌性角膜炎的表达、定位、细胞来源，通过阻断实验及过表达实验进一步分析DC-SIGN对中性粒细胞募集、真菌杀灭、抗炎及促炎细胞因子、Th细胞分化和细胞凋亡的影响。分析DC-SIGN通路各环节及与TLR4、Dectin-1、LOX-1和Mincle等真菌相关受体的影响，确定DC-SIGN在免疫调控中的重要意义，论证DC-SIGN在真菌性角膜炎的免疫调控作用以及机体微环境对其功能的影响。分析DC-SIGN基因遗传学及DNA甲基化改变对发病及病程的影响，在此基础上分析雷帕霉素等免疫抑制剂是否通过调节DC-SIGN发挥免疫调控作用，进一步解释真菌性角膜炎致病机制，为真菌性角膜炎的治疗提供新思路。

Fungal keratitis (FK) is a severe blindness causing disease. Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), as a pattern recognition receptor, can recognize the pathogen-associated molecular patterns of fungi. This research intends to analyze the immune regulation role of DC-SIGN. First, we will detect the expression and source of DC-SIGN in fungal keratitis. And then explore the effect of DC-SIGN on neutrophils infiltration, fungi killing, apoptosis and the balance of pro- and anti-inflammatory cytokines and the balance of Th cells differention by the methods of confocal microscopy, Western blot, ELISA, Real-time PCR, and flow cytometry et al. Analyze the relationships among DC-SIGN and downstream pathways. We will detect the effect of DC-SIGN on TLR4, Dectin-1, LOX-1 and Mincle pathways and determine the special significance of DC-SIGN in the complex network and the importance of host immune condition. Explore the influence of DC-SIGN DNA methylation and genetic polymorphism in antifungal immunity of cornea and the influence of rapamycin on DC-SIGN. Observe the influence of immunosuppressant such as Rapamycin on DC-SIGN in the course of fungal keratitis. Provide new idea of immunomodulation for the treatment of fungal keratitis.