CCR4 and its ligands: from bench to bedside.
Chemokines and chemokine receptors orchestrate cell migration and homing in the body. Humans have at least 44 chemokines that are further classified into four subfamilies based on the N-terminal conserved cysteine motifs: CXC, CC, C and CX3C. All the known chemokine receptors are seven transmembrane-type receptors. Humans have 18 chemotactic and 5 atypical non-chemotactic (recycling or scavenging) receptors. CC chemokine receptor 4 (CCR4) is the receptor for two CC chemokine ligands (CCLs)-CCL17 (also called thymus- and activation-regulated chemokine) and CCL22 (macrophage-derived chemokine). Among the various T-cell subsets, CCR4 is predominantly expressed by Th2 cells, cutaneous lymphocyte antigen-positive skin-homing T cells and Treg cells. Thus, CCR4 attracts much attention for its possible clinical applications in diseases involving these T-cell subsets. Furthermore, CCR4 is often highly expressed by mature T-cell neoplasms such as adult T-cell leukemia/lymphoma (ATL) and cutaneous T-cell lymphomas (CTCLs). This article is a brief overview of basic and clinical research on CCR4 and its ligands, which has eventually led to the development of a humanized defucosylated anti-CCR4 antibody 'Mogamulizumab' for treatment of relapsed/refractory ATL and CTCLs.
['Yoshie|Osamu|O|', 'Matsushima|Kouji|K|']
D000818:Animals D061067:Antibodies, Monoclonal, Humanized D002465:Cell Movement D054414:Chemokine CCL17 D054422:Chemokine CCL22 D006801:Humans D007167:Immunotherapy D015459:Leukemia-Lymphoma, Adult T-Cell D008024:Ligands D016410:Lymphoma, T-Cell, Cutaneous D054398:Receptors, CCR4 D050378:T-Lymphocytes, Regulatory D018418:Th2 Cells D057170:Translational Research, Biomedical
CCR4 Th2 ATL allergy regulatory T cell