CCL5

CCL5, also known as regulated upon activation, normal T cell expressed and secreted (RANTES), is a chemokine in the CC class. It is a small secreted protein that functions as a chemoattractant, guiding various immune cells to sites of inflammation. The gene CCL5 encodes this cytokine in humans; it is produced by T lymphocytes, natural killer cells, monocytes, platelets, and endothelial cells after activation.

Chemokine activity: CCL5 signals primarily through the G protein-coupled receptors CCR1, CCR3, and CCR5, promoting chemotaxis and activation of T cells, eosinophils, basophils, and NK cells. It also binds to glycosaminoglycans such as heparan sulfate on cell surfaces, helping to create chemokine gradients.

Physiological and disease roles: CCL5 participates in host defense against pathogens and in wound healing. It is implicated in allergic inflammation and asthma, and has been associated with atherosclerosis and other inflammatory conditions. Elevated levels are observed in several autoimmune and infectious diseases.

Clinical significance: In the context of HIV, CCL5 can interact with CCR5, which is used by R5-tropic strains for entry. It can modulate viral infection or replication. The CCL5-CCR5 axis is a focus of therapeutic research. No approved therapies use CCL5 itself, but CCR5 antagonists are used or studied.

Structure and genetics: CCL5 is a member of the CC chemokine family, characterized by adjacent cysteine residues near the N-terminus. The mature human CCL5 protein is about 68 amino acids long with a disulfide-bonded structure.

Research and therapeutic prospects: Efforts to modulate CCL5 signaling aim to reduce pathological leukocyte recruitment in inflammatory diseases, but clinical translation is limited by redundancy and overlapping chemokine networks.