CCR4 and its ligands: from bench to bedside
CCR4 and its ligands: from bench to bedside
复制标题
DOI：
10.1093/intimm/dxu079
复制
发表时间：
2015-01-01
影响因子：
4.4
通讯作者：
Matsushima, Kouji
中科院分区：
文献类型：
--
作者：
Yoshie, Osamu;Matsushima, Kouji
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端保守半胱氨酸基序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是七种跨膜型受体。人类有18个趋化受体和5个非典型的非趋化受体（回收或清除）。CC趋化因子受体4 （CCR4）是两种CC趋化因子配体（CCLs）的受体- ccl17（也称为胸腺和激活调节趋化因子）和CCL22（巨噬细胞源趋化因子）。在各种T细胞亚群中，CCR4主要由T(h)2细胞、皮肤淋巴细胞抗原阳性皮肤归巢T细胞和T-reg细胞表达。因此，CCR4在涉及这些t细胞亚群的疾病中可能的临床应用备受关注。此外，CCR4通常在成熟t细胞肿瘤中高表达，如成人t细胞白血病/淋巴瘤（ATL）和皮肤t细胞淋巴瘤（CTCLs）。本文简要概述了CCR4及其配体的基础和临床研究，这些研究最终导致了人源化去聚焦抗CCR4抗体Mogamulizumab的开发，用于治疗复发/难治性ATL和ctcl。
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 T(h)2 cells, cutaneous lymphocyte antigen-positive skin-homing T cells and T-reg 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.