Th17和Treg细胞与蕈样肉芽肿相关性研究

Association analysis between T helper type 17 cells, regulatory T cells and mycosis fungoides

目的 探讨调节性T（Treg）细胞和Th17细胞在蕈样肉芽肿不同分期中的变化.方法 流式细胞仪检测28例蕈样肉芽肿、13例大斑块型副银屑病、17例扁平苔藓患者及10例健康对照外周血Treg细胞和Th17细胞百分率,同时应用免疫组化法检测40例蕈样肉芽肿、13例副银屑病、17例扁平苔藓及10例健康对照蜡块组织中叉头状转录因子P3（FOXP3）和白细胞介素17（IL-17）的表达.结果 蕈样肉芽肿、副银屑病、扁平苔藓患者外周血Treg细胞百分率分别为（8.09±1.68）％,（6.53±1.67）％,（2.84±1.16）％较健康对照[（1.01±0.35）％]升高,差异均有统计学意义.蕈样肉芽肿、副银屑病患者外周血Treg细胞百分率亦高于扁平苔藓（均P＜ 0.05）;蕈样肉芽肿与副银屑病患者差异无统计学意义（P＞0.05）.外周血Th17细胞百分率在蕈样肉芽肿较副银屑病、扁平苔藓患者比健康人升高[（3.22±0.82）％比（2.46±0.79）％,（1.38±0.47）％和（0.59±0.30）％,均P＜ 0.05].FOXP3阳性率在蕈样肉芽肿、副银屑病及扁平苔藓均高于正常皮肤组织[（14.94±4.46）％,（11.95±4.72）％,（6.32±2.81）％比（3.43±1.79）％,均P＜ 0.05],蕈样肉芽肿及副银屑病比扁平苔藓高（均P＜ 0.05）,蕈样肉芽肿比副银屑病差异无统计学意义（P＞0.05）.IL-17阳性率在蕈样肉芽肿、副银屑病、扁平苔藓和正常组织中分别为（15.89±177;4.27）％,（12.02±177;3.34）％,（4.84±177;1.93）％和（2.62±177;0.89）％,其中,蕈样肉芽肿均高于副银屑病、扁平苔藓组织及正常组织（均P＜ 0.05）.蕈样肉芽肿、副银屑病外周血Th 17/Treg细胞比率比扁平苔藓、健康对照低（0.41±177;0.11,0.39±177;0.12比0.50±177;0.06,0.57±177;0.19（均P＜0.05）.早期蕈样肉芽肿Th17细胞与Treg细胞呈正相关（r=0.423,P＜ 0.05）,肿瘤期蕈样肉芽肿Th17细胞有所下降,而Treg细胞继续升高,但蕈样肉芽肿各期差异无统计学意义,且二者在肿瘤期无相关性.结论 Treg和Th17细胞失衡可能参与了蕈样肉芽肿的发生与发展.

Objective To investigate the changes of T helper type 17 （Thl7） cells and regulatory T （Treg） cells in different stages of mycosis fungoides.Methods Flow cytometry was performed to determine the percentage of Treg and Th17 cells in peripheral blood from 28 patients with mycosis fungoides （MF）,13 patients with large plaque parapsoriasis （PP）,17 patients with lichen planus （LP） and 10 healthy human controls,and immunohistochemistry to detect the expressions of forkhead box protein 3 （FOXP3） and interleukin （IL）-17 in tissue specimens from 40 patients with MF,13 with PP,17 with LP and 10 healthy human controls.Statistical analysis was carried out by one-way analysis of variance and Pearson correlation analysis.Results As far as the percentage of Treg cells in peripheral blood was concerned,MF,PP and LP patients were significantly higher than the healthy controls （8.09% ±177; 1.68%,6.53% ±177; 1.67% and 2.84 % ±177; 1.16% vs.1.01% ±177; 0.35,all P〈 0.05）,PP patients were higher than LP patients and healthy controls （both P 〈 0.05）,and LP patients were higher than healthy controls （P 〈 0.05）.The percentage of Th17 cells in peripheral blood was significantly increased in MF patients compared with PP patients,LP patients and healthy controls （3.22% ±177; 0.82% vs.2.46% ±177; 0.79%,1.38% ±177; 0.47% and 0.59% ±177; 0.30%,all P 〈 0.05）.Elevated expression rate of FOXP3 was observed in MF,PP and LP lesions as compared with normal skin （14.94% ±177; 4.46%,11.95% ±177; 4.72%,6.32% ±177; 2.81% vs.3.43% ±177; 1.79%,all P 〈 0.05）,and in MF and PP lesions compared with LP lesions （both P 〈 0.05）,but no significant difference was observed between MF and PP lesions （P 〉 0.05）.There was a significant increase in the expression rate of IL-17 in MF lesions compared with PP lesions,LP lesions and normal skin （15.89% ±177; 4.27% vs.12.02% ±177; 3.34%,4.84% ±177; 1.93% and 2.62% ±177; 0.89%,all P 〈 0.05）.The Th17/Treg ratio in peripheral blood was significantly lower in MF and PP patients than in LP patients and healthy controls （0.41 ±177; 0.11 and 0.39 ±177; 0.12 vs.0.50 ±177; 0.06 and 0.57 ±177; 0.19,all P 〈 0.05）.A positive correlation was observed between the proportion of Thl7 cells and Treg cells （r =0.423,P 〈 0.05） in patients with early-stage MF,but not in those with tumor-stage MF.The proportion of Th17 cells decreased,but that of Treg cells continuously increased in patients with tumor-stage MF.However,no significant difference was noted in the proportion of Thl7 cells or Treg cells among patients with different stages of MF.Conclusion The imbalance between Treg and Th17 cells may be involved in the occurrence and development of MF.