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首页> 美国卫生研究院文献>Medicina >Upregulated Expression of Macrophage Migration Inhibitory Factor Its Analogue D-Dopachrome Tautomerase and the CD44 Receptor in Peripheral CD4 T Cells from Clinically Isolated Syndrome Patients with Rapid Conversion to Clinical Defined Multiple Sclerosis
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Upregulated Expression of Macrophage Migration Inhibitory Factor Its Analogue D-Dopachrome Tautomerase and the CD44 Receptor in Peripheral CD4 T Cells from Clinically Isolated Syndrome Patients with Rapid Conversion to Clinical Defined Multiple Sclerosis

机译：巨噬细胞迁移抑制因子其类似物D-多巴色素互变异构酶和CD44受体在临床分离的综合征患者中迅速转变为临床定义的多发性硬化症的外周CD4 T细胞中的表达上调。

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: Macrophage Migration Inhibitory Factor (MIF) and D-Dopachrome Tautomerase (DDT) are two pleiotropic and primarily, but not exclusively, proinflammatory cytokines belonging to the MIF family of cytokines that have recently been shown to be implicated in the pathogenesis of progressive forms of human progressive Multiple Sclerosis (MS) and the experimental model counterpart in rodents. We have presently evaluated a transcriptomic analysis of the expression of MIF, DDT, their receptors CD74 and CD44, and MIF co-receptors CXCR2, CXCR4, and CXCR7 in peripheral blood of patients with Clinically Isolated Syndrome (CIS), with rapid progression to clinical defined MS. Our analysis reveals that MIF, DDT, and CD44 are overexpressed in CD4 T cells from patients with CIS, as compared to healthy controls. Accordingly, a significant overlap was observed between the genes overexpressed in CD4 T cells from patients with CIS and the genes belonging to the MIF regulatory network. This upregulated expression appeared to be unique for CD4 T cells, as other immune cells including CD8 T cells, B cells, and monocytes from these patients exhibited expression levels of these molecules that were superimposable to those observed in healthy controls. Overall, our data suggest that the overexpression MIF cytokine family signature may occur in CD4 T cells from patients with CIS, and that this phenomenon may be implicated in the pathogenesis of the disease, offering the possibility to represent both a diagnostic marker and a therapeutic target.
机译：：巨噬细胞迁移抑制因子（MIF）和D-多巴色素互变异构酶（DDT）是两种多效性的，主要但非排他性地，属于MIF细胞因子家族的促炎细胞因子，最近被证明与渐进形式的MIF的发病机理有关。人类进行性多发性硬化症（MS）和啮齿动物的实验模型对应物。我们目前已经评估了临床分离综合征（CIS）患者外周血中MIF，DDT，其受体CD74和CD44以及MIF共同受体CXCR2，CXCR4和CXCR7的表达的转录组学分析，并迅速发展为临床定义的MS。我们的分析表明，与健康对照相比，MIF，DDT和CD44在CIS患者的CD4 T细胞中过表达。因此，在来自患有CIS的患者的CD4T细胞中过表达的基因与属于MIF调节网络的基因之间观察到明显的重叠。这种上调的表达对于CD4 T细胞似乎是独特的，因为来自这些患者的其他免疫细胞（包括CD8 T细胞，B细胞和单核细胞）表现出的这些分子的表达水平可与健康对照者观察到的水平叠加。总体而言，我们的数据表明，来自CIS患者的CD4 T细胞中可能发生过表达MIF细胞因子家族信号，并且这种现象可能与疾病的发病机制有关，从而有可能代表诊断标志物和治疗靶标。

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