Chemerin在葡萄膜炎发生中的作用及机制研究

Chemerin is a novel chemoattractant protein. It can modulate immune system through recruiting immune cells such as dendritic cells which express Chemerin receptor: ChemR23. Dendritic cells are known to be involved in the pathogenesis of uveitis. We found that Chemerin in ankylosing spondylitis patients with acute anterior uveitis was significantly lower than normal controls, and Chemerin has a inhibitory effect on the inflammtory factors secreted by dendritic cells such as IL-1β、IL-8、TNF-α in ankylosing spondylitis patients with acute anterior.uveitis. Thus we speculate that Chemerin may participate in the development of uveitis through regulating the function of dendritic cells. To confirm this hypothesis, we will focus on the influence of Chemerin on the function of dendritic cells. This study may contribute novel biological markers and treatment targets.

Chemerin是近年来新发现的一种趋化蛋白，通过招募表达ChemR23受体的免疫细胞，例如树突细胞，从而调控免疫应答，而树突细胞与葡萄膜炎发病关系密切。最近我们发现强直性脊柱炎伴发活动性前葡萄膜炎患者血清Chemerin含量较正常对照低，且Chemerin对AS伴AAU患者树突细胞分泌的炎性因子IL-1β、IL-8、TNF-α有明显的抑制作用。据此推测Chemerin可能通过调控树突细胞参与葡萄膜炎发病。为证实此假设，本研究将探讨Chemerin对树突细胞功能的影响，揭示Chemerin通过何种机制参与葡萄膜炎发生，为葡萄膜炎个体化防治提供新的靶点。

强直性脊柱炎（AS）伴发的急性前葡萄膜炎（AAU）是一类常见的致盲性眼病，DC细胞诱导的CD4+T细胞免疫反应是该病发生的重要机制。最近研究发现Chemerin可调控免疫反应。预实验已发现AS伴AAU的患者，Chemerin水平显著下降。本研究以此为切入点，探讨AS伴AAU患者Chemerin的水平，与患者体内异常的DC细胞和CD4+T细胞免疫反应的相关性，明确Chemerin是否与失调的免疫反应相关；探讨Chemerin对DC诱导CD4+T细胞分化及功能的作用及分子机制，确定其参与疾病发生的具体机制；利用动物模型探讨Chemerin对动物葡萄膜炎发生、严重程度及转归的影响及对局部和全身免疫反应的作用。通过上诉研究，将有望获得Chemerin参与AS伴发AAU的直接证据，进一步阐明AS伴AAU的发病机理，为该病的预防和治疗研究提供新方向。