趋化素样因子1参与红斑狼疮病理过程的机制研究

The infiltration of inflammatory cell is an important factor in the pathogenic mechanism in SLE, mainly causing tissue damage. Inflammtory chemokines can recruit and activate leukocytes, which is a crucial cause in tissue damage of the autoimune process. The chemokine-like factor 1 is a novel human cytokine which has chemotaxis effect on different leukocytes both in vitro and in vivo. CKLF1 is a novel functional ligand for CCR4. CKLF1 is also found that it is up-regulated in activated CD4+、CD8+T cells. Those data suggest that CKLF1 may play an important role in the pathogenesis of lupus.In this study, we evaluated the expression of CKLF1 in skin, kidney and peripheral blood mononuclear cells of patients.Overexpression by recombinant eukaryotic expression plasmid in lupus mice to probe into roles of CKLF1 in the development of SLE.Then we we investigated the ligants of CKLF1 through experiments in vitro.At last confirm the effect of CKLF1 by its antagonist C19 peptide.The objective of our investigations is clear the role of CKLF1 in pathogenic of tissue damage in SLE and develop new drug aim at pupus.

炎症细胞浸润在系统性红斑狼疮(SLE) 的发病机制中发挥重要作用，炎症性趋化因子对特异白细胞的趋化和功能活化是启动与自身免疫反应有关的关键步骤。趋化素样因子1（CKLF1）是一个新发现的趋化因子，可趋化中性粒细胞、淋巴细胞、单核细胞，CKLF1在活化的T细胞表达上调，因此我们推测，CKLF1与自身免疫性疾病病理过程密切相关。本课题拟通过对狼疮患者皮损、肾损及外周血细胞的检测，初步明确CKLF1在狼疮中的表达情况及其来源；通过动物模型研究CKLF1过表达对狼疮鼠的影响；进一步通过体外实验确定CKLF1的配体，及其发挥作用的途径；最后利用其拮抗肽C19证实CKLF1在狼疮组织损伤中的作用。旨在阐明CKLF1参与狼疮病理过程中的作用及机制，开发新的有效治疗药物。