Fractalkine在风湿病治疗中的新作用。

IF 6.2 Q1 IMMUNOLOGY ImmunoTargets and Therapy Pub Date : 2020-11-04 eCollection Date: 2020-01-01 DOI:10.2147/ITT.S277991
Yoshiya Tanaka, Kana Hoshino-Negishi, Yoshikazu Kuboi, Fumitoshi Tago, Nobuyuki Yasuda, Toshio Imai
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引用次数: 9

摘要

类风湿性关节炎(RA)是一种影响关节的自身免疫性疾病,其特征是滑膜增生和骨质侵蚀,并伴有新生血管和促炎细胞的浸润。在过去的20年里,生物疾病修饰抗风湿药物的引入极大地改变了类风湿性关节炎的治疗。然而,不到50%的RA患者进入缓解期,10-15%的患者难以治疗。目前尚无治疗类风湿性关节炎的方法。Fractalkine (FKN,也称为CX3CL1)是一种细胞膜结合的趋化因子,可以诱导激活血管内皮细胞。FKN具有细胞粘附分子和化学引诱剂的双重功能。FKN特异性结合趋化因子受体CX3CR1, CX3CR1在免疫细胞亚群(如巡逻单核细胞和杀伤淋巴细胞)上选择性表达。FKN-CX3CR1轴被认为在炎症级联的启动中起重要作用,并可能导致炎症性疾病中组织损伤的加剧。因此,动物模型研究表明,抑制FKN-CX3CR1轴不仅可以改善风湿性疾病,还可以减少相关并发症,如肺纤维化和心血管疾病。最近,一种人源化抗fkn单克隆抗体E6011在一项针对RA患者的2期临床试验(NCT02960438)中显示出有希望的疗效,具有剂量依赖性的临床反应和良好的安全性。总之,临床前和临床结果表明,E6011可能通过抑制炎症的主要因素和减轻伴随的心血管和纤维化疾病,代表了风湿病的一种新的治疗方法。在这篇综述中,我们描述了FKN-CX3CR1轴在风湿病中的作用以及抗fkn单克隆抗体的治疗潜力,以满足未满足的临床需求。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Emerging Role of Fractalkine in the Treatment of Rheumatic Diseases.

Rheumatoid arthritis (RA) is an autoimmune disorder that affects joints and is characterized by synovial hyperplasia and bone erosion associated with neovascularization and infiltration of proinflammatory cells. The introduction of biological disease-modifying anti-rheumatic drugs has dramatically changed the treatment of RA over the last 20 years. However, fewer than 50% of RA patients enter remission, and 10-15% are treatment refractory. There is currently no cure for RA. Fractalkine (FKN, also known as CX3CL1) is a cell membrane-bound chemokine that can be induced on activated vascular endothelial cells. FKN has dual functions as a cell adhesion molecule and a chemoattractant. FKN binds specifically to the chemokine receptor CX3CR1, which is selectively expressed on subsets of immune cells such as patrolling monocytes and killer lymphocytes. The FKN-CX3CR1 axis is thought to play important roles in the initiation of the inflammatory cascade and can contribute to exacerbation of tissue injury in inflammatory diseases. Accordingly, studies in animal models have shown that inhibition of the FKN-CX3CR1 axis not only improves rheumatic diseases but also reduces associated complications, such as pulmonary fibrosis and cardiovascular disease. Recently, a humanized anti-FKN monoclonal antibody, E6011, showed promising efficacy with a dose-dependent clinical response and favorable safety profile in a Phase 2 clinical trial in patients with RA (NCT02960438). Taken together, the preclinical and clinical results suggest that E6011 may represent a new therapeutic approach for rheumatic diseases by suppressing a major contributor to inflammation and mitigating concomitant cardiovascular and fibrotic diseases. In this review, we describe the role of the FKN-CX3CR1 axis in rheumatic diseases and the therapeutic potential of anti-FKN monoclonal antibodies to fulfill unmet clinical needs.

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来源期刊
CiteScore
16.50
自引率
0.00%
发文量
7
审稿时长
16 weeks
期刊介绍: Immuno Targets and Therapy is an international, peer-reviewed open access journal focusing on the immunological basis of diseases, potential targets for immune based therapy and treatment protocols employed to improve patient management. Basic immunology and physiology of the immune system in health, and disease will be also covered.In addition, the journal will focus on the impact of management programs and new therapeutic agents and protocols on patient perspectives such as quality of life, adherence and satisfaction.
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