Therapeutic intervention of inflammatory/immune diseases by inhibition of the fractalkine (CX3CL1)-CX3CR1 pathway.
Therapeutic intervention of inflammatory/immune diseases by inhibition of the fractalkine (CX3CL1)-CX3CR1 pathway.
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DOI：
10.1186/s41232-016-0017-2
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发表时间：
2016
影响因子：
8.1
通讯作者：
Yasuda N
中科院分区：
文献类型：
--
作者：
Imai T;Yasuda N
炎症和免疫反应是由局部产生的选择性入侵和积累到病变部位的免疫细胞。免疫细胞从血液经血管内皮细胞向组织浸润的过程受到多种趋化因子和细胞粘附分子的密切调控。Fractalkine (FKN)/CX3CL1是一种具有趋化因子/粘蛋白杂交结构和跨膜结构域的膜结合趋化因子，具有粘附分子和趋化剂的双重功能。FKN主要在活化的内皮细胞、活化的成纤维细胞和成骨细胞上表达。其受体CX3CR1在细胞毒性效应淋巴细胞、单核/巨噬细胞和破骨细胞上表达。到目前为止，已经确定了fk - cx3cr1轴的许多关键功能方面：(1)免疫细胞对血管内皮细胞的快速捕获和牢固粘附，(2)趋化性，(3)增强向其他趋化因子的转运，(4)在血管内皮细胞上巡逻的单核细胞的爬行行为，(5)单核细胞作为炎症内皮的辅助细胞来招募炎症细胞的保留，以及(6)巨噬细胞的存活。本文就FKN在类风湿关节炎（RA）中的病理作用及FKN在破骨细胞分化中的生理作用作一综述。此外，我们将讨论抗fkn mAb对RA患者的治疗潜力及其与其他细胞因子抑制剂不同的作用模式。
Inflammatory and immune responses are generated locally by the selective invasion and accumulation of the immune cells into the lesion site. The infiltration process of the immune cells into the tissue from the blood through the vascular endothelial cells is closely regulated by a number of chemotactic factors and cell adhesion molecules. Fractalkine (FKN)/CX3CL1 is a membrane-bound chemokine possessing a chemokine/mucin hybrid structure and a transmembrane domain and has a dual function as an adhesion molecule and a chemoattractant. FKN is mainly expressed on activated endothelial cells, activated fibroblasts, and osteoblasts. Its receptor, CX3CR1, is expressed on cytotoxic effector lymphocytes, monocytes/macrophages, and osteoclasts. To date, a lot of key functional aspects of the FKN-CX3CR1 axis has been identified: (1) the rapid capture and firm adhesion of immune cells to vascular endothelial cells, (2) chemotaxis, (3) the enhancement of the transmigration to other chemokines, (4) the crawling behavior of the monocytes that patrol on vascular endothelial cells, (5) the retention of monocytes as the accessory cells of the inflamed endothelium to recruit inflammatory cells, and (6) the survival of the macrophage. In this review, we will focus on the pathological role of FKN in rheumatoid arthritis (RA) and the physiological role of FKN on osteoclast differentiation. Furthermore, we will discuss the therapeutic potential of anti-FKN mAb for RA patients and its distinct mode of action from other cytokine inhibitors.
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影响因子：
--
作者：
Nanki, T;Imai, T;Miyasaka, N
通讯作者：
Miyasaka, N
DOI：
10.1161/atvbaha.111.237412
发表时间：
2012-03-01
影响因子：
8.7
作者：
White, Gemma E.;Greaves, David R.
通讯作者：
Greaves, David R.
DOI：
10.1084/jem.20101474
发表时间：
2010-12-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ishii M;Kikuta J;Shimazu Y;Meier-Schellersheim M;Germain RN
通讯作者：
Germain RN
DOI：
10.1186/ar115
发表时间：
2000
期刊：
Arthritis research
影响因子：
--
作者：
McInnes IB;Leung BP;Liew FY
通讯作者：
Liew FY
影响因子：
64.8
作者：
Bazan, JF;Bacon, KB;Schall, TJ
通讯作者：
Schall, TJ