Enhanced IL-6/phosphorylated STAT3 signaling is related to the imbalance of circulating T follicular helper/T follicular regulatory cells in patients with rheumatoid arthritis.
Enhanced IL-6/phosphorylated STAT3 signaling is related to the imbalance of circulating T follicular helper/T follicular regulatory cells in patients with rheumatoid arthritis.
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IL-6/磷酸化 STAT3 信号传导增强与类风湿性关节炎患者循环滤泡辅助性 T/滤泡调节性细胞失衡有关
DOI：
10.1186/s13075-018-1690-0
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发表时间：
2018-08-29
影响因子：
4.9
通讯作者：
Wang LL
中科院分区：
文献类型：
--
作者：
Niu Q;Huang ZC;Wu XJ;Jin YX;An YF;Li YM;Xu H;Yang B;Wang LL
滤泡辅助性T（Tfh）细胞专门帮助B淋巴细胞，其在具有主要B细胞组分的自身免疫性疾病（例如类风湿性关节炎（RA））中发挥核心作用。卵泡调节性T细胞（Follicular Regulatory T，Tfr）控制着生发中心Tfh和B细胞的过度活化。Tfh细胞和Tfr细胞的失调已被报道参与一些自身免疫性疾病的发病机制。然而，Tfh和Tfr细胞的平衡及其在RA发生发展中的作用尚不清楚。在这项研究中，我们招募了44例RA患者（20例活动期RA患者和24例非活动期RA患者）和20名健康对照，并分析了循环Tfh和Tfr细胞的频率，Tfh细胞中程序性死亡-1（PD-1）、诱导型共刺激分子（ICOS）、细胞内IL-21和pSTAT 3的表达，以及血清IL-6水平。并分析了这些参数之间的相关性以及Tfh或Tfr细胞与疾病活动性的相关性。RA患者（尤其是活动期RA）Tfh细胞频率较高，但Tfr细胞百分比较低，从而导致Tfh/Tfr比值升高。RA患者Tfh细胞中PD-1和IL-21的表达水平高于健康受试者，而患者和对照组之间未观察到ICOS表达差异。RA患者血清IL-6水平与pSTAT 3表达均升高，且两者呈正相关。此外，pSTAT 3表达与Tfh细胞频率呈正相关。28个关节中基于C反应蛋白的疾病活动性评分（DAS 28-CRP）与Tfr细胞频率呈负相关，但与Tfh/Tfr比值和PD-1表达呈正相关。结果表明，增强的IL-6/pSTAT 3信号可能有助于促进Tfh细胞，从而使Tfh与Tfr细胞的比例发生偏移，这可能是RA疾病进展的关键。本文的在线版本（10.1186/s13075-018-1690-0）包含补充材料，可供授权用户使用。
Follicular helper T (Tfh) cells are specialized in helping B lymphocytes, which play a central role in autoimmune diseases that have a major B cell component, such as in rheumatoid arthritis (RA). Follicular regulatory T (Tfr) cells control the over-activation of Tfh and B cells in germinal centers. Dysregulation of Tfh cells and Tfr cells has been reported to be involved in the pathogenesis of some autoimmune diseases. However, the balance of Tfh and Tfr cells, and their roles in the development and progression of RA are still not clear. In this study, we enrolled 44 patients with RA (20 patients with active RA and 24 patients with inactive RA) and 20 healthy controls, and analyzed the frequencies of circulating Tfh and Tfr cells, expression of programmed death-1 (PD-1), inducible co-stimulator (ICOS), intracellular IL-21, and pSTAT3 in Tfh cells, and serum levels of IL-6. The correlation among these parameters and that of Tfh or Tfr cells with disease activity were also analyzed. Patients with RA (especially active RA) had higher frequencies of Tfh cells, but lower percentages of Tfr cells, thereby resulting in elevated ratios of Tfh/Tfr. Expression levels of PD-1 and IL-21 in Tfh cells were higher in patients with RA than in healthy subjects, while no difference in ICOS expression was observed between patients and controls. Both pSTAT3 expression and serum IL-6 levels increased in patients with RA, and positive correlation between them was observed. Additionally, pSTAT3 expression was positively correlated with Tfh cell frequency. The Disease Activity Score in 28 joints based on C-reactive protein (DAS28-CRP) was negatively correlated with Tfr cell frequency, but was positively correlated with both Tfh/Tfr ratio and PD-1 expression. Results demonstrated that enhanced IL-6/pSTAT3 signaling may contribute to promotion of Tfh cells, consequently skewing the ratio of Tfh to Tfr cells, which may be crucial for disease progression in RA. The online version of this article (10.1186/s13075-018-1690-0) contains supplementary material, which is available to authorized users.
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影响因子：
--
作者：
Jiang H;Cui N;Yang L;Liu C;Yue L;Guo L;Wang H;Shao Z
通讯作者：
Shao Z
影响因子：
32.4
作者：
Nurieva, Roza I.;Chung, Yeonseok;Hwang, Daehee;Yang, Xuexian O.;Kang, Hong Soon;Ma, Li;Wang, Yi-Hong;Watowich, Stephanie S.;Jetten, Anton M.;Tian, Qiang;Dong, Chen
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影响因子：
20.3
作者：
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通讯作者：
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T细胞特异性CXCR5缺乏可防止类风湿关节炎。
影响因子：
4.6
作者：
Moschovakis GL;Bubke A;Friedrichsen M;Falk CS;Feederle R;Förster R
通讯作者：
Förster R
尖端：循环静脉曲张通过IL-6产生诱导人T卵泡细胞的分化。
DOI：
10.4049/jimmunol.1401190
发表时间：
2015-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Chavele KM;Merry E;Ehrenstein MR
通讯作者：
Ehrenstein MR