Ranasinghe Ranmali, Eri Rajaraman
School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, Tasmania 7250, Australia.
Medicines (Basel). 2018 Jul 2;5(3):69. doi: 10.3390/medicines5030069.
C-C chemoattractant cytokine (chemokine) receptor 6 (CCR6) and its exclusive binding molecule CCL20 is an extremely important chemokine receptor-ligand pair which controls cell migration and immune induction during inflammatory disease. Not many scientific studies have been undertaken to study its immune mechanisms in detail, but its unique contribution to steady state cell chemotaxis in upholding immune tolerance and regulating immune homeostasis during inflammation is evident in multiple systems in the human body, including skin, liver, lung, kidney, brain, eye, joints, gonads and the gut. The role of CCR6 is constitutively expressed as a series of much debilitating severe inflammatory and autoimmune diseases, Human Immunodeficiency Virus (HIV) and cancer metastasis. CD4⁺ T cells, the central organizers of adaptive immunity, are stringently mobilized by the CCR6/CCL20 axis also induced by cytokines and a host of other factors in a carefully executed immune modulation scenario, to bring about a delicate balance between inflammation inducing T17 cells and regulatory T cells. Although the exact immune regulatory role is not elucidated as yet, the CCR6/CCL20 axis is implicated as a front runner which determines the polarization of T17 and regulatory T cells, upon which depends the resolution or progression of many debilitating disorders. This review therefore aims at emphasizing the pleiotropic significance of the chemokines CCR6 and CCL20 in immunologic function in multiple organ systems, thereby hoping to accentuate its value in future therapeutic modalities.
C-C趋化因子细胞因子(趋化因子)受体6(CCR6)及其唯一结合分子CCL20是一对极其重要的趋化因子受体-配体,在炎症性疾病中控制细胞迁移和免疫诱导。尚未开展许多科学研究来详细探究其免疫机制,但其在维持免疫耐受和调节炎症期间的免疫稳态方面对稳态细胞趋化性的独特贡献在人体的多个系统中都很明显,包括皮肤、肝脏、肺、肾脏、大脑、眼睛、关节、性腺和肠道。CCR6的作用在一系列严重的衰弱性炎症和自身免疫性疾病、人类免疫缺陷病毒(HIV)和癌症转移中持续表达。CD4⁺T细胞作为适应性免疫的核心组织者,在精心执行的免疫调节过程中,也受到细胞因子和许多其他因素诱导的CCR6/CCL20轴的严格动员,从而在诱导炎症的T17细胞和调节性T细胞之间实现微妙的平衡。尽管确切的免疫调节作用尚未阐明,但CCR6/CCL20轴被认为是决定T17细胞和调节性T细胞极化的前沿因素,许多衰弱性疾病的消退或进展都取决于此。因此,本综述旨在强调趋化因子CCR6和CCL20在多个器官系统免疫功能中的多效性意义,从而希望突出其在未来治疗方式中的价值。