Fibrocyte and T cell interactions promote disease pathogenesis in rheumatoid arthritis
Fibrocyte and T cell interactions promote disease pathogenesis in rheumatoid arthritis
复制标题
DOI：
10.1016/j.jaut.2016.02.008
复制
发表时间：
2016-05-01
影响因子：
12.8
通讯作者：
Fish, Eleanor N.
中科院分区：
文献类型：
--
作者：
Galligan, Carole L.;Keystone, Edward C.;Fish, Eleanor N.
风湿性关节炎（RA）是一种全身性自身免疫性疾病。我们以前确定了一个循环细胞群，纤维细胞，这是激活疾病的早期。由于RA的特征在于自身抗体和自身反应性T细胞的形成，其通常先于症状发作，因此这些研究的目的是表征T细胞活化背景下的纤维细胞活化。多维流式细胞术被用来表征外周血（PB）纤维细胞和T细胞的活化状态，来自不同水平的疾病活动性RA患者。与健康对照相比，RA患者的纤维细胞表现出增加的活化，表示为升高的STAT 3和NF-κ B磷酸化水平。与健康对照组相比，RA患者循环中活化的Th 17细胞和T细胞数量较高，中度至高度疾病活动性患者的Th 17细胞数量较高。此外，在疾病更严重的RA患者中观察到FOXP 3 + ROR γ t+双阳性CD 4 + T细胞数量增加。我们的数据证实，RA中循环纤维细胞扩增，活化纤维细胞数量增加与CD 4 + T细胞数量增加之间存在直接相关性。此外，我们的数据表明，循环纤维细胞和活化的T细胞之间的相互作用可能会促进疾病的活动。具体而言，我们提供了体外证据表明，小鼠来源的CD 4 + T细胞产生GM-CSF，诱导纤维细胞增殖。反过来，活化的纤维细胞产生IL-6，促进Th 17极化。(C)2016爱思唯尔有限公司版权所有
Rheumatoid arthritis (RA) is a systemic autoimmune disease. We previously identified a circulating cell population, fibrocytes, which is activated early in disease. As RA is characterized by the formation of autoantibodies and autoreactive T cells, which often precede symptom onset, the objective of these studies was to characterize fibrocyte activation in the context of T cell activation. Multidimensional flow cytometry was used to characterize the activation status of peripheral blood (PB) fibrocytes and T cells derived from RA patients with different levels of disease activity. Compared to healthy controls, fibrocytes from RA patients exhibited increased activation, denoted as elevated levels of phosphorylation of STAT3 and NF-kappa B. RA patients had higher numbers of circulating activated Th17 cells and Tregs compared with healthy controls, Th17 cell numbers being higher in patients with moderate to high disease activity. Additionally, increased numbers of FOXP3+ ROR gamma t+ double positive CD4+ T cells were observed in RA patients with more severe disease. Our data confirm that circulating fibrocytes are expanded in RA and that there is a direct correlation between the increase in number of activated fibrocytes and increased number of CD4+ T cells. Moreover, our data suggest that interactions-between circulating fibrocytes and activated T cells may promote disease activity. Specifically, we provide in vitro evidence that mouse derived CD4+ T cells produce GM-CSF which induces fibrocyte proliferation. In turn, activated fibrocytes produce IL-6, promoting Th17 polarization. (C) 2016 Elsevier Ltd. All rights reserved.