The role of fractalkine (CX3CL1) in regulation of CD4+ cell migration to the central nervous system in patients with relapsing-remitting multiple sclerosis

The role of fractalkine (CX3CL1) in regulation of CD4+ cell migration to the central nervous system in patients with relapsing-remitting multiple sclerosis
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DOI:
10.1016/j.clim.2015.01.001
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发表时间:
2015-04-01
影响因子:
8.6
通讯作者:
Markovic-Plese, Silva
Markovic-Plese, Silva
中科院分区:
医学3区
文献类型:
--
作者:
Blauth, Kevin;Zhang, Xin;Markovic-Plese, Silva

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Fractalkine(CX3CL1)在临床隔离综合征(CIS)患者的脑脊液(CSF)以及复发-缓解型多发性硬化症(RRMS)患者的脑脊液和血清样本中水平升高。RRMS患者外周血中CD4(+)T细胞表达其表面受体(CX3CR1)和细胞内黏附分子(ICAM-1)的百分率明显高于健康对照组(HCS)。RRMS患者脑脊液中CX3CR1(+)、ICAM-1(+)、CD4(+)T细胞明显增多。体外迁移研究表明,向CX3CL1梯度迁移的CD4(+)T细胞比非迁移细胞表达更高水平的ICAM-1。CX3CL1可显著增加RRMS患者外周血中CD4(+)T细胞的干扰素-γ和肿瘤坏死因子-α基因的表达及干扰素-α的分泌。CX3CL1上调RRMS患者来源的但不是HC来源的CD4(+)T细胞表面ICAM-1的表达。因此,在MS(C)2015 Elsevier Inc.的早期炎症反应中,CX3CL1诱导CX3CR1(+)ICAM-1(+)CD4(+)T细胞招募到中枢神经系统(CNS)。保留所有权利。
Fractalkine (CX3CL1) levels are increased in the cerebrospinal fluid (CSF) of patients with clinically isolated syndrome (CIS), as well as in the CSF and serum samples from patients with relapsing-remitting multiple sclerosis (RRMS). A higher percentage of circulating CD4(+) T-cells expressed its surface receptor (CX3CR1) and intracellular adhesion molecule (ICAM-1) in RRMS patients in comparison to healthy controls (HCs). The CX3CR1(+)ICAM-1(+)CD4(+) T-cells are enriched in the CSF of the RRMS patients. In vitro migration studies revealed that CD4(+) T-cells, which migrated toward a CX3CL1 gradient, expressed higher levels of ICAM-1 than non-migrating cells. CX3CL1 significantly increased IFN-gamma and TNF-alpha gene expression and IFN-gamma secretion by CD4(+) T-cells derived from the RRMS patients. CX3CL1 upregulated ICAM-1 expression on the surface of RRMS patient-derived but not HC-derived CD4(+) T-cells. Thus, CX3CL1 induces recruitment of CX3CR1(+)ICAM-1(+)CD4(+) T-cells into the central nervous system (CNS) during the early inflammatory response in MS. (C) 2015 Elsevier Inc. All rights reserved.