Jiang Nan, Li Mengtao, Zeng Xiaofeng
Department of Internal Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.
Chin Med J (Engl). 2014;127(20):3557-61.
Systemic sclerosis (SSc) is an autoimmune disease that has three major components: inflammation, fibrosis, and vasculopathy. T-helper 17 cell (Th17) and regulatory T cell (Treg) are considered to be critical for autoimmune disease pathogenesis. The role of Th17 and Treg in SSc is still unclear. The aim of this study was to detect the presence of Th17s and CD4(+)CD25(+) Tregs in peripheral blood samples from SSc patients and to investigate the possible roles of these two T cell subsets in SSc pathogenesis.
Th17s (CD4 and IL-17 positive) and CD4(+)CD25(+) Tregs (CD4, CD25 and Foxp3 positive) in the peripheral blood mononuclear cells of 53 SSc patients and 27 healthy controls were counted by flow cytometry. The differences between SSc and control patients were analyzed. Clinical parameters, including disease duration, duration of the second symptoms, Modified Rodnan Skin Score (MRSS), anti-topoisomerase I antibody, anti-U1 ribonucleoprotein (RNP) antibody, systemic involvements, pulmonary function test (PFT) and high resolution computed tomography (HRCT) score were prospectively collected following EUSTAR (EULAR scleroderma trial and research group) protocols. The correlations between the experimental and clinical data were investigated.
The ratio of Th17 in SSc patients was significantly elevated compared to healthy controls (8.74% vs. 4.41%, P < 0.001). The amount of Th17 was positively correlated with disease duration (R = 0.531, P = 0.013) and duration of the second symptoms (R = 0.505, P = 0.023). The ratio of CD4(+)CD25(+) Treg in SSc patients also significantly differed from the healthy controls (3.04% vs. 2.24%, P = 0.018). Elevated Tregs were more frequently observed in patients with a high interstitial lung disease (ILD) score on computed tomography (24/36) compared with patients with normal ILD scores (4/12, P = 0.043). Elevated Tregs were also more often observed in patients with low carbon monoxide diffusing capacity (DLCO) (24/34) compared with patients with normal DLCO (4/11, P = 0.042).
T cell abnormalities are remarkable in systemic sclerosis. Th17s proliferate and their numbers increase with lengthened disease duration. Th17s might participate in both inflammation and fibrosis by secreting IL-17. CD4(+)CD25(+) Tregs also proliferate in SSc and may play important roles in promoting fibrosis.
系统性硬化症（SSc）是一种自身免疫性疾病，具有炎症、纤维化和血管病变三个主要成分。辅助性T细胞17（Th17）和调节性T细胞（Treg）被认为对自身免疫性疾病的发病机制至关重要。Th17和Treg在SSc中的作用仍不清楚。本研究的目的是检测SSc患者外周血样本中Th17和CD4(+)CD25(+) Treg的存在情况，并探讨这两个T细胞亚群在SSc发病机制中的可能作用。
采用流式细胞术对53例SSc患者和27例健康对照者外周血单个核细胞中的Th17（CD4和IL-17阳性）和CD4(+)CD25(+) Treg（CD4、CD25和Foxp3阳性）进行计数。分析SSc患者与对照患者之间的差异。按照EUSTAR（欧洲抗风湿病联盟硬皮病试验和研究组）方案前瞻性收集临床参数，包括病程、第二症状持续时间、改良Rodnan皮肤评分（MRSS）、抗拓扑异构酶I抗体、抗U1核糖核蛋白（RNP）抗体、全身受累情况、肺功能测试（PFT）和高分辨率计算机断层扫描（HRCT）评分。研究实验数据与临床数据之间的相关性。
与健康对照相比，SSc患者中Th17的比例显著升高（8.74%对4.41%，P < 0.001）。Th17的数量与病程（R = 0.531，P = 0.013）和第二症状持续时间（R = 0.505，P = 0.023）呈正相关。SSc患者中CD4(+)CD25(+) Treg的比例也与健康对照有显著差异（3.04%对2.24%），P = 0.018）。与计算机断层扫描ILD评分正常的患者（4/12）相比，ILD评分高的患者（24/36）中Treg升高更为常见（P = 0.043）。与一氧化碳弥散量（DLCO）正常的患者（4/11）相比，DLCO低的患者（24/34）中Treg升高也更为常见（P = 0.042）。
系统性硬化症中T细胞异常显著。Th17随着病程延长而增殖且数量增加。Th17可能通过分泌IL-17参与炎症和纤维化过程。CD4(+)CD25(+) Treg在SSc中也会增殖，并可能在促进纤维化中发挥重要作用。
