RANTES/CCL5

CCL5, also known as RANTES (Regulation of Activation, Expression and Secretion by Normal T Cells), belongs to the CC subfamily of chemokines. In human, the CCL5 gene is located in the q11.2-q12 region of human chromosome 17 and encodes CCL5 a protein with a molecular weight of 8 kDa. CCL5 can be expressed by T cells, monocytes, NK cells, epithelial cells, fibroblasts, and CCL5 can bind to receptors CCR1, CCR3, CCR4 and CCR5, with the highest affinity for CCR5^[1]. CCL5 binding to CCR5 leads to phosphorylation of phosphatidylinositol 3-kinase ( PI3K ), and the phosphorylated PI3K further acidifies protein kinase B on serine 473, and the Akt/PKB complex phosphorylates and inactivates the serine/threonine protein kinase GSK-3. In parallel, CCL5 binding to CCR5 induces Bcl2 protein expression, which promotes cell apoptosis. CCL5 can also act as a potential agonist for the G protein-coupled receptor GPR75, which, together with GPR75, may play a role in neuronal survival by activating downstream signaling pathways involving PI3, Akt, and MAP kinases, and in insulin secretion by pancreatic islet cells by activating GPR75^[2]. In addition to acting as a chemotactic agent, CCL5 is also a major HIV suppressor produced by CD⁸⁺ T cells. It is involved in inflammation maintenance, transplantation, antiviral immunity, tumor development, and many human diseases and disorders such as viral hepatitis or COVID-19^[3].