Miyabe Yoshishige, Miyabe Chie, Iwai Yoshiko, Luster Andrew D
Department of Cell Biology, Institute for Advanced Medical Sciences, Nippon Medical School, Tokyo, Japan.
Department of Dermatology, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
JMA J. 2020 Jul 15;3(3):182-192. doi: 10.31662/jmaj.2020-0019. Epub 2020 Jul 13.
Arrest of circulating leukocytes and subsequent diapedesis is a fundamental component of inflammation. In general, the leukocyte migration cascade is tightly regulated by chemoattractants, such as chemokines. Chemokines, small secreted chemotactic cytokines, as well as their G-protein-coupled seven transmembrane spanning receptors, control the migratory patterns, positioning and cellular interactions of immune cells. Increased levels of chemokines and their receptors are found in the blood and within inflamed tissue in patients with rheumatoid arthritis (RA) and vasculitis. Chemokine ligand-receptor interactions regulate the recruitment of leukocytes into tissue, thus contributing in important ways to the pathogenesis of RA and vasculitis. Despite the fact that blockade of chemokines and chemokine receptors in animal models have yielded promising results, human clinical trials in RA using inhibitors of chemokines and their receptors have generally failed to show clinical benefits. However, recent early phase clinical trials suggest that strategies blocking specific chemokines may have clinical benefits in RA, demonstrating that the chemokine system remains a promising therapeutic target for rheumatic diseases, such as RA and vasuculitis and requires further study.
循环白细胞的滞留及随后的渗出是炎症的一个基本组成部分。一般来说，白细胞迁移级联反应受趋化因子（如趋化因子）的严格调控。趋化因子是一类分泌型小趋化细胞因子，及其G蛋白偶联的七跨膜受体，控制着免疫细胞的迁移模式、定位和细胞间相互作用。在类风湿关节炎（RA）和血管炎患者的血液及炎症组织中，趋化因子及其受体水平升高。趋化因子配体-受体相互作用调节白细胞向组织的募集，从而在RA和血管炎的发病机制中发挥重要作用。尽管在动物模型中阻断趋化因子和趋化因子受体已取得了有前景的结果，但在RA患者中使用趋化因子及其受体抑制剂的人体临床试验总体上未能显示出临床益处。然而，最近的早期临床试验表明，阻断特定趋化因子的策略可能对RA有临床益处，这表明趋化因子系统仍然是RA和血管炎等风湿性疾病的一个有前景的治疗靶点，需要进一步研究。
