CCR2 is a chemokine receptor that binds monocyte chemoattractant proteins (MCP-1, 2, 3 and 4). Two spliced variants were initially described for CCR2 (CCR2A and CCR2B). These variants differ in their terminal carboxyl tails. Monocyte adhesion to the arterial endothelium and subsequent migration into the intima are central events in the pathogenesis of atherosclerosis. CCR2 and MCP-1 have been associated to atherosclerotic plaques. MCP-1 is induced by modified-LDL in endothelial cells and may trigger firm adhesion of monocytes to vascular endothelium under flow conditions. Local overexpression of MCP-1 at vessel walls induces infiltration of macrophages and formation of atherosclerotic lesions. Obesity induces an inflammatory state that is implicated in many clinically important complications, including insulin resistance, diabetes, atherosclerosis, and non-alcoholic fatty liver disease. CCR2 influences the development of obesity and associated adipose tissue inflammation.
CD193, also known as CC-chemokine receptor 3 (CCR3), CC CKR3, MIP1-alpha receptor like-2, and eotaxin receptor, is a member of the G protein-coupled seven transmembrane receptors family. It binds to the CC chemokines eotaxin, eotaxin-2, and eotaxin-3 with high affinity. CCR3 has also been reported to bind RANTES, MCP-3, and MCP-4 with low affinity. CCR3 receptor is expressed on human eosinophils, basophils, mast cells, mononuclear phagocytes, platelets, CD34+ hematopoietic progenitor cells, Th2-like lymphocytes, and keratinocytes. CCR3 is thought to play a role in allergic diseases such as bronchial asthma and allergic rhinitis. CCR3 is a co-receptor for HIV-1 and HIV-2, and the binding of eotaxin with CCR3 has been shown to inhibit HIV infection in some cell types.
CD194, also known as CCR4, is a CC chemokine receptor. It binds CCL17 and CCL22 and is expressed on a subset of T and B cells, basophils, monocytes, and NK cells. Human Th2 cells are characterized by the expression of CCR4 and CCR8, and these receptors are regulated differently during Th2 development. Human peripheral blood Tregs can be divided into two distinct populations based on the expression of CCR4. Freshly isolated Tregs express CCR4 and presumably represent memory-type Tregs, and CCR4- Tregs require CD3-mediated activation to acquire a regulatory activity. Depletion of CCR4+ T cells leads to Th1-type polarization of CD4+ T cells and augmentation of CD8+ T cell responses to tumor antigens. CCR4 and its ligands are important for the recruitment of memory T cells into the skin in various cutaneous immune diseases.
CD195, also known as CCR5, is a 45 kD G protein-coupled seven transmembrane CC-chemokine receptor. It binds to MIP-1α, MIP-1β, and RANTES and is expressed on a subset of T cells and monocytes. CD195 mediates an intracellular signal thought to induce cell differentiation and proliferation. CCR5 has also been shown to act as a co-receptor for R5 HIV-1 cell entry; modification of CCR5 by sulfation contributes to the efficiency of HIV-1 entry. Recent studies have shown CCR5 to play a role in a variety of other human diseases, ranging from infectious and inflammatory diseases to cancer.
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