Differential expression of CD11c by peripheral blood NK cells reflects temporal activity of multiple sclerosis
Differential expression of CD11c by peripheral blood NK cells reflects temporal activity of multiple sclerosis
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DOI：
10.4049/jimmunol.177.8.5659
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发表时间：
2006-10-15
影响因子：
4.4
通讯作者：
Yamamura, Takashi
中科院分区：
文献类型：
--
作者：
Aranami, Toshimasa;Miyake, Sachiko;Yamamura, Takashi
多发性硬化症（MS）是一种自身免疫性疾病，表现出很大程度的变化，在时间的疾病活动。我们最近已经证明，外周血NK细胞分泌IL-5（NK 2偏见）-与MS的缓解状态相关。在这项研究中，我们报告MS患者在缓解期差异表达NK细胞表面CD 11 c（操作定义为CD 11 c（高）或CD 11 c（低））。当我们比较CD 11 c（高）或CD 11 c（低）患者时，在CD 11 c（低）患者中观察到NK细胞中IL-5和加塔-3的表达，这些细胞被认为赋予疾病保护性NK 2表型，但在CD 11 c（高）患者中未观察到。相反，CD 11 c（高）组显示NK细胞上HLA-DR的表达更高。体外研究表明，NK细胞刺激性细胞因子如IL-15可上调NK细胞上的CD 11 c表达。鉴于先前的证据显示MS中促炎细胞因子水平升高与暂时性疾病活动之间存在关联，我们推测炎症信号可能在诱导CD 11 c（高）NK细胞表型中发挥作用。一个新的患者队列的随访显示，10名CD 11 c（高）MS患者中有6名在评估后120天内出现临床复发，而13名CD 11 c（低）MS患者中只有2名出现疾病加重（p = 0.003）。因此，NK细胞上CD 11 c的较高表达可能反映了MS的时间活性以及调节性NK 2表型的丧失，这可能使我们能够将其用作监测MS患者免疫状态的潜在生物标志物。
Multiple sclerosis (MS) is an autoimmune disease, showing a great degree of variance in temporal disease activity. We have recently demonstrated that peripheral blood NK cells biased for secreting IL-5 (NK2 bias)-are associated with the remission state of MS. In this study, we report that MS patients in remission differentially express CD11c on NK cell surface (operationally defined as CD11c(high) or CD11c(low)). When we compared CD11c(high) or CD11c(low) patients, the expression of IL-5 and GATA-3 in NK cells supposed to endow a disease-protective NK2 phenotype was observed in CD11c(low) but not in CD11c(high) patients. In contrast, the CD11c(high) group showed a higher expression of HLA-DR on NK cells. In vitro studies demonstrated that NK cell stimulatory cytokines such as IL-15 would up-regulate CD11c expression on NK cells. Given previous evidence showing an association between an increased level of proinflammatory cytokines and temporal disease activity in MS, we postulate that inflammatory signals may play a role in inducing the CD11c(high) NK cell phenotype. Follow-up of a new cohort of patients showed that 6 of 10 CD11c(high) MS patients developed a clinical relapse within 120 days after evaluation, whereas only 2 of 13 CD11c(low) developed exacerbated disease (p = 0.003). As such, a higher expression of CD11c on NK cells may reflect the temporal activity of MS as well as a loss of regulatory NK2 phenotype, which may allow us to use it as a potential biomarker to monitor the immunological status of MS patients.