Department of Pharmacy, The Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin 214400, China.
Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Centre of Anti-Inflammatory and Immune Medicine, Center of Rheumatoid Arthritis of Anhui Medical University, Hefei 230032, China.
Int Immunopharmacol. 2023 Aug;121:110431. doi: 10.1016/j.intimp.2023.110431. Epub 2023 Jun 16.
Chemokine receptor 7 (CCR7) is a G protein-coupled receptor containing 7 transmembrane domains that is expressed on various cells, such as naive T/B cells, central memory T cells, regulatory T cells, immature/mature dendritic cells (DCs), natural killer cells, and a minority of tumor cells. Chemokine ligand 21 (CCL21) is the known high-affinity ligand that binds to CCR7 and drives cell migration in tissues. CCL21 is mainly produced by stromal cells and lymphatic endothelial cells, and its expression is significantly increased under inflammatory conditions. Genome-wide association studies (GWAS) have shown a strong association between CCL21/CCR7 axis and disease severity in patients with rheumatoid arthritis, sjogren's syndrome, systemic lupus erythematosus, polymyositis, ankylosing spondylitis, and asthma. Disrupting CCL21/CCR7 interaction with antibodies or inhibitors prevents the migration of CCR7-expressing immune and non-immune cells at the site of inflammation and reduces disease severity. This review emphasizes the importance of the CCL21 /CCR7 axis in autoimmune diseases and evaluates its potential as a novel therapeutic target for these conditions.
趋化因子受体 7（CCR7）是一种 G 蛋白偶联受体，包含 7 个跨膜结构域，在各种细胞上表达，如幼稚 T/B 细胞、中央记忆 T 细胞、调节性 T 细胞、未成熟/成熟树突状细胞（DC）、自然杀伤细胞和少数肿瘤细胞。趋化因子配体 21（CCL21）是已知的高亲和力配体，与 CCR7 结合并驱动组织中的细胞迁移。CCL21 主要由基质细胞和淋巴内皮细胞产生，在炎症条件下其表达显著增加。全基因组关联研究（GWAS）表明 CCL21/CCR7 轴与类风湿关节炎、干燥综合征、系统性红斑狼疮、多发性肌炎、强直性脊柱炎和哮喘患者的疾病严重程度之间存在强烈关联。用抗体或抑制剂阻断 CCL21/CCR7 相互作用可阻止 CCR7 表达的免疫和非免疫细胞在炎症部位迁移，并降低疾病严重程度。本文强调了 CCL21/CCR7 轴在自身免疫性疾病中的重要性，并评估了其作为这些疾病新型治疗靶点的潜力。
