Chemokine receptor type-5: a key regulator of immunity, disease pathogenesis, and emerging therapeutic target

CCR5 (C–C chemokine receptor type 5) is a critical chemokine receptor involved in immune cell migration, signaling, and inflammation. Expressed on T lymphocytes, macrophages, and dendritic cells, it regulates leukocyte recruitment to inflamed sites via ligands such as CCL3, CCL4, and CCL5. Beyond immune regulation, CCR5 is implicated in diseases like rheumatoid arthritis, inflammatory bowel disease, and atherosclerosis, where the CCL5/CCR5 axis exacerbates inflammation and tissue damage. In cancer, CCR5 promotes tumor growth, metastasis, and immune evasion, particularly in aggressive breast cancer subtypes (basal and HER-2 +). It also serves as a co-receptor for HIV entry, with the CCR5Δ32 mutation conferring resistance. With therapeutic inhibition of CCR5 gaining attention, Maraviroc is approved for HIV treatment, while monoclonal antibodies such as leronlimab, genetic strategies (CRISPR), and dual CCR2/CCR5 antagonists such as cenicriviroc are under investigation for broader applications. Blocking CCR5 has shown efficacy in reducing metastasis and improving chemotherapy outcomes, reinforcing its therapeutic potential. Along with CCR5’s role in disease pathogenesis, emphasizing its involvement in immune regulation and inflammatory processes, this review explores the multifaceted role of CCR5 in immunity, its contribution to disease pathogenesis, and innovative therapeutic interventions targeting CCR5 to modulate immune responses and treat diseases.