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Ⅱ期肺结节病患者调节性 T 细胞 - Th17 细胞平衡的广泛紊乱。

Extensively disturbance of regulatory T cells - Th17 cells balance in stage II pulmonary sarcoidosis.

机构信息

Department of Respiratory Medicine, Jiangsu Key Laboratory of Molecular Medicine, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.

Center of Translational Medicine, Jiangsu Key Laboratory of Molecular Medicine, Nanjing University Medical School, Nanjing, China.

出版信息

Int J Med Sci. 2017 Sep 4;14(11):1136-1142. doi: 10.7150/ijms.18838. eCollection 2017.

DOI:10.7150/ijms.18838
PMID:29104468
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5666545/
Abstract

BACKGROUND

Sarcoidosis is a systemic inflammatory disorder characterized by granulomas. Not enough evidences correlate the derangement of CD4+ T subsets, which have an impact on the therapeutic effects of corticosteroids, with the radiographical staging of sarcoidosis. Here we show the disturbance of CD4+ T subsets in newly diagnosed stage II pulmonary sarcoidosis, which is the most common stage in which corticosteroids treatment is used.

MATERIALS AND METHODS

39 newly diagnosed and treatment-naïve patients and 9 subjects after corticosteroids treatment were included. CD4+ CD45RA+/ CD45RO+ cells, CCR4+ CCR6+ cells, and T regulatory cells (Tregs) were tested by Flow Cytometry Analysis. Th1/Th2, Tregs/Th17 related cytokines and mRNAs, SAA and CCL20 were also measured. The activation of PI3K/PTEN/Akt signaling pathway was detected.

RESULTS

Percentages of CD4+CD45RO+ memory T cells and Tregs, serum levels of IL-17A, TGF-β1, IL-6, IFN-γ, IL-10, SAA and CCL20, copies of T-bet, FoxP3, IL-17 and RORc in the periphery were elevated in newly diagnosed stage II pulmonary sarcoidosis patients. Additionally, PI3K/Akt signaling pathway was activated in bronchoalveolar lavage fluid cells.

CONCLUSIONS

Disturbance of T memory cells, Th1/Th2, and Tregs/Th17 cells, and activation of PI3K/Akt signaling were seen in newly diagnosed stage II pulmonary sarcoidosis, which can be partly ameliorated by corticosteroids treatment.

摘要

背景

结节病是一种以肉芽肿为特征的系统性炎症性疾病。目前尚缺乏足够的证据表明，CD4+T 亚群的紊乱与结节病的放射分期有关，而 CD4+T 亚群对皮质类固醇的治疗效果有影响。在这里，我们展示了新诊断的 II 期肺结节病中 CD4+T 亚群的紊乱，这是最常见的使用皮质类固醇治疗的阶段。

材料和方法

纳入 39 例新诊断且未经皮质类固醇治疗的患者和 9 例皮质类固醇治疗后的患者。通过流式细胞术分析检测 CD4+CD45RA+/CD45RO+细胞、CCR4+CCR6+细胞和 T 调节细胞（Tregs）。还测量了 Th1/Th2、Tregs/Th17 相关细胞因子和 mRNAs、SAA 和 CCL20。检测了 PI3K/PTEN/Akt 信号通路的激活情况。

结果

新诊断的 II 期肺结节病患者外周血中 CD4+CD45RO+记忆 T 细胞和 Tregs 的百分比、血清中 IL-17A、TGF-β1、IL-6、IFN-γ、IL-10、SAA 和 CCL20 的水平、外周血中 T-bet、FoxP3、IL-17 和 RORc 的拷贝数均升高。此外，在支气管肺泡灌洗液细胞中激活了 PI3K/Akt 信号通路。

结论

在新诊断的 II 期肺结节病中观察到 T 记忆细胞、Th1/Th2 和 Tregs/Th17 细胞的紊乱以及 PI3K/Akt 信号通路的激活，皮质类固醇治疗可部分改善这些紊乱。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24f3/5666545/f87b13041875/ijmsv14p1136g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24f3/5666545/0d5102a87f2f/ijmsv14p1136g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24f3/5666545/ec3757b4cecc/ijmsv14p1136g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24f3/5666545/651f120864ad/ijmsv14p1136g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24f3/5666545/f87b13041875/ijmsv14p1136g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24f3/5666545/0d5102a87f2f/ijmsv14p1136g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24f3/5666545/ec3757b4cecc/ijmsv14p1136g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24f3/5666545/651f120864ad/ijmsv14p1136g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24f3/5666545/f87b13041875/ijmsv14p1136g004.jpg

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