Yoshie Osamu, Matsushima Kouji
Department of Microbiology, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka 589-8511, Japan
Department of Molecular Preventive Medicine, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Int Immunol. 2015 Jan;27(1):11-20. doi: 10.1093/intimm/dxu079. Epub 2014 Aug 2.
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.
趋化因子和趋化因子受体在体内协调细胞迁移和归巢。人类至少有44种趋化因子，根据N端保守的半胱氨酸基序可进一步分为四个亚家族：CXC、CC、C和CX3C。所有已知的趋化因子受体都是七跨膜型受体。人类有18种趋化性受体和5种非典型非趋化性（循环或清除）受体。CC趋化因子受体4（CCR4）是两种CC趋化因子配体（CCL）——CCL17（也称为胸腺和活化调节趋化因子）和CCL22（巨噬细胞衍生趋化因子）的受体。在各种T细胞亚群中，CCR4主要由Th2细胞、皮肤淋巴细胞抗原阳性的皮肤归巢T细胞和调节性T细胞表达。因此，CCR4因其在涉及这些T细胞亚群的疾病中的潜在临床应用而备受关注。此外，CCR4在成熟T细胞肿瘤如成人T细胞白血病/淋巴瘤（ATL）和皮肤T细胞淋巴瘤（CTCL）中通常高度表达。本文简要概述了关于CCR4及其配体的基础和临床研究，这些研究最终促成了一种用于治疗复发/难治性ATL和CTCL的人源化去岩藻糖基化抗CCR4抗体“莫加穆利单抗”的研发。
