Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Nat Rev Rheumatol. 2019 Dec;15(12):731-746. doi: 10.1038/s41584-019-0323-6. Epub 2019 Nov 8.
Chemokines, a family of small secreted chemotactic cytokines, and their G protein-coupled seven transmembrane spanning receptors control the migratory patterns, positioning and cellular interactions of immune cells. The levels of chemokines and their receptors are increased in the blood and within inflamed tissue of patients with rheumatic diseases, such as rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, vasculitis or idiopathic inflammatory myopathies. Chemokine ligand-receptor interactions control the recruitment of leukocytes into tissue, which are central to the pathogenesis of these rheumatic diseases. Although the blockade of various chemokines and chemokine receptors has yielded promising results in preclinical animal models of rheumatic diseases, human clinical trials have, in general, been disappointing. However, there have been glimmers of hope from several early-phase clinical trials that suggest that sufficiently blocking the relevant chemokine pathway might in fact have clinical benefits in rheumatic diseases. Hence, the chemokine system remains a promising therapeutic target for rheumatic diseases and requires further study.
趋化因子是一族小分子分泌型趋化细胞因子，其 G 蛋白偶联的七跨膜受体可控制免疫细胞的迁移模式、定位和细胞间相互作用。在类风湿性关节炎、系统性红斑狼疮、系统性硬化症、血管炎或特发性炎性肌病等风湿性疾病患者的血液和炎症组织中，趋化因子及其受体的水平升高。趋化因子配体-受体相互作用控制白细胞向组织中的募集，这是这些风湿性疾病发病机制的核心。虽然在风湿性疾病的临床前动物模型中阻断各种趋化因子和趋化因子受体已取得了有希望的结果，但总体而言，人类临床试验令人失望。然而，从几项早期临床试验中出现了一线希望，表明充分阻断相关趋化因子途径实际上可能对风湿性疾病具有临床益处。因此，趋化因子系统仍然是风湿性疾病有前途的治疗靶点，需要进一步研究。
