Objective: To investigate the Th17 cell and Treg cell levels in patients with sarcoidosis, and their relation to disease activation and glucocorticoids treatment.
Methods: Twenty-three sarcoidosis patients admitted in Yinzhou People's Hospital from January 2009 to December 2013 and 25 healthy subjects (controls) were included in this study. The blood samples and bronchoalveolar lavage fluid (BALF) samples were collected in all patients before and after glucocorticoids treatment. The serum angiotensin converting enzyme (SACE) levels were detected. The percentages of Th17 cells and Treg cells in peripheral blood and BALF were determined by flow cytometry, the concentrations of cytokines in serum and supernatants of BALF were measured by enzyme-linked immunosorbent assay (ELISA). The levels of ROR-γt and Foxp3 mRNA transcripts in peripheral blood mononuclear cells (PBMC) were determined by real-time quantitative PCR. The potential correlation between the percentages of Th17 or Treg cells and SACE levels was evaluated.
Results: Compared with healthy controls, significantly higher frequencies of Th17 cells (4.34%±0.89% vs 1.60% ± 0.42%), lower frequencies of Treg cells (1.28% ± 0.37% vs 3.39% ± 0.50%) in peripheral blood were observed. Higher level of ROR-γt mRNA (21.31 ± 3.55 vs 3.63 ± 1.00) and lower level of Foxp3 mRNA (1.60 ± 0.24 vs 3.12 ± 0.76) in peripheral blood were detected in sarcoidosis patients in active stage (before glucocorticoids treatment) (all P<0.01). After the treatment of glucocorticoids, these index in peripheral blood were significantly improved (Th17 cells 2.16% ± 0.68%，Treg cells 2.21% ± 0.42%, ROR-γt mRNA 10.15 ± 1.93, Foxp3 mRNA 2.44 ± 0.38) ( all P<0.05). The changing trends of Th17 and Treg cell cytokines levels in serum were consistent with two type cells. Meanwhile, the changing trends of above index in BALF of patients treated by glucocorticoids were consistent with those in sarcoidosis patients in active stage. The increased ratios of Th17 cells to Treg cells were positively correlated with the level of serum SACE (r= 0.781).
Conclusion: The imbalance of Th17 cells and Treg cells in peripheral blood and airway may be involved in the pathogenesis of sarcoidosis, which was associated with the activity of disease, and the treatment of glucocorticoids may achieve a therapeutic effect by correcting the immune imbalance.
目的: 观察结节病患者辅助性T细胞17（Th17）和调节性T细胞（Treg）的变化及与疾病活动的关系。
方法: 选择2009年1月~2013年12月在鄞州人民医院治疗的23例结节病患者作为研究对象，以25例健康志愿者作为正常对照组，在糖皮质激素治疗前后分别用酶反应连续监测法测定血清血管紧张素转化酶（SACE），流式细胞术测定外周血和支气管肺泡灌洗液（BALF）中Th17细胞和Treg细胞比例，酶联免疫吸附试验法测定血清及BALF上清液中相关细胞因子水平，实时荧光定量PCR测定外周血转录因子ROR-γt和Foxp3 mRNA表达水平，分析Th17/Treg比值与病情活动的相关性。
结果: 结节病患者活动期外周血Th17细胞比例较正常对照组明显升高（4.34%±0.89% vs 1.60%±0.42%），而Treg细胞比例明显降低（1.28%±0.37% vs 3.39%±0.50%）；转录因子ROR-γt mRNA表达水平较正常对照组明显升高（21.31±3.55 vs 3.63±1.00），而Foxp3 mRNA明显降低（1.60±0.24 vs 3.12±0.76），差异均有统计学意义（均 P＜0.01）。糖皮质激素治疗后上述指标均显著改善（外周血Th17细胞比例2.16%±0.68%，Treg细胞比例2.21%±0.42%，转录因子ROR-γt mRNA水平10.15±1.93，Foxp3 mRNA水平2.44±0.38），差异均有统计学意义（均 P＜0.05）。外周血Th17和Treg细胞相关细胞因子的变化与两类细胞比例变化一致；激素治疗后BALF中上述指标变化趋势与外周血一致。Th17/Treg细胞比值与外周血SACE水平呈显著正相关（r=0.781， P＜0.01）。
结论: Th17/Treg细胞平衡失调与结节病的活动密切相关，可能参与了结节病的发病过程。