Lacotte Stéphanie, Brun Susana, Muller Sylviane, Dumortier Hélène
CNRS, Institut de Biologie Moléculaire et Cellulaire, Immunologie et Chimie Thérapeutiques, Strasbourg, France.
Ann N Y Acad Sci. 2009 Sep;1173:310-7. doi: 10.1111/j.1749-6632.2009.04813.x.
CXCR3 is a G protein-coupled, seven-transmembrane receptor that binds and is activated by the three IFN-gamma-inducible chemokines of the CXC family named CXCL9, CXCL10, and CXCL11. These chemokines are not constitutively expressed but are up-regulated in a proinflammatory cytokine milieu. Consequently, their major function is to selectively recruit immune cells at inflammation sites, but they also play a role in angiogenesis mechanisms. In the last few years, strong experimental and clinical evidence has been obtained supporting the idea that the CXCR3 pathway is involved in the development of autoimmune diseases, especially by creating local amplification loops of inflammation in target organs, thereby inducing worsening of clinical manifestations. This article briefly reviews what we know today about the nature and functions of CXCR3, with special emphasis on its involvement in two main rheumatic systemic autoimmune diseases, namely rheumatoid arthritis and systemic lupus erythematosus.
CXCR3是一种G蛋白偶联的七跨膜受体，它能结合CXC家族的三种干扰素γ诱导趋化因子CXCL9、CXCL10和CXCL11并被其激活。这些趋化因子并非组成性表达，而是在促炎细胞因子环境中上调。因此，它们的主要功能是在炎症部位选择性募集免疫细胞，但它们在血管生成机制中也发挥作用。在过去几年中，已经获得了强有力的实验和临床证据，支持CXCR3途径参与自身免疫性疾病发展的观点，特别是通过在靶器官中形成局部炎症放大环，从而导致临床表现恶化。本文简要回顾了我们目前对CXCR3的性质和功能的了解，特别强调了它在两种主要的风湿性全身性自身免疫性疾病，即类风湿性关节炎和系统性红斑狼疮中的作用。
