CCL21/CCR7 axis as a therapeutic target for autoimmune diseases

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.