title: CCR4 and its ligands: from bench to bedside.
abstract: 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.
authors.affiliation: Department of Microbiology, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka 589-8511, Japan o.yoshie@med.kindai.ac.jp.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yoshie
authors.affiliation: Department of Molecular Preventive Medicine, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D002465:Cell Movement; D054414:Chemokine CCL17 / Q000819:agonists; D054422:Chemokine CCL22 / Q000819:agonists; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology / Q000628:therapy*; D008024:Ligands; D016410:Lymphoma, T-Cell, Cutaneous / Q000276:immunology / Q000628:therapy*; D054398:Receptors, CCR4 / Q000819:agonists* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D057170:Translational Research, Biomedical
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D008024:Ligands; D054398:Receptors, CCR4; C549035:mogamulizumab
keywords: ATL; CCR4; Th2; allergy; regulatory T cell