转录因子RORγτ和FOXP3在口腔扁平苔藓病损组织中的表达及意义

上海口腔医学 ›› 2014, Vol. 23 ›› Issue (4): 472-476.

转录因子RORγτ和FOXP3在口腔扁平苔藓病损组织中的表达及意义

谢三祥¹, 丰琳², 朱声荣¹, 丁蕾¹

1.华中科技大学同济医学院附属同济医院口腔医学中心,湖北武汉 430030;
2.湖北省黄冈市妇幼保健院检验科,湖北黄冈 438000

收稿日期:2013-09-26 出版日期:2014-08-20 发布日期:2014-10-20
通讯作者: 丁蕾,Tel:027-83663805,E-mail:lding@hust.edu.cn
作者简介:谢三祥(1978-), 男, 主治医师, E-mail:xisix@163.com

Expressions of RORγτ and FOXP3 and clinical significance in patients with oral lichen planus

XIE San-xiang¹, FENG Lin², ZHU Sheng-rong¹, DING Lei¹

1.Center of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. Wuhan 430030;
2. Laboratory Medicine, Maternal and Child Health Hospital. Huanggang 438000, Hubei Province, China

Received:2013-09-26 Online:2014-08-20 Published:2014-10-20

摘要/Abstract

摘要： 目的:口腔扁平苔藓(oral lichen planus,OLP)是一种发生于口腔黏膜的T淋巴细胞介导的自身免疫性疾病。辅助性T细胞(helper T lymphocytes, Th)在OLP的发病过程中具有重要作用,本研究旨在进一步探索OLP患者局部病损组织中辅助性T细胞亚群Th17细胞和Treg细胞的作用。方法:纳入43例OLP患者和13例健康志愿者。采用实时定量PCR法检测局部病损组织中Th17和Treg细胞的特征性转录因子RORγτ和FOXP3的表达,采用GraphPad Prism 5 软件对其表达差异进行统计学分析。结果:OLP局部病损组织中转录因子RORγτ和FOXP3的表达显著高于正常黏膜组织,而且均与OLP的临床分型密切相关。萎缩糜烂型OLP组病损组织中RORγτ/FOXP3比值显著高于网状型OLP组和健康对照组,而网状型OLP组的RORγτ/FOXP3比值虽然高于对照组,但差异无显著性。结论:Th17细胞和Treg细胞均参与OLP的局部免疫反应;同时,Th17/Treg失衡也参与了重症型OLP的致病过程,且表现为Th17细胞优势。

关键词: FOXP3, RORγτ, Th17, Treg, 口腔扁平苔藓

Abstract: PURPOSE: Oral lichen planus was considered as T cell mediated autoimmune disease affecting oral mucosa with unknown etiopathogenesis. Helper T lymphocytes played an important role in the pathogenesis of OLP. The purpose of this study was to investigate the possible role of Th17 and Treg cells in OLP lesions. METHODS: Forty three patients with OLP (24 patients with reticular OLP and 19 patients with atrophic-erosive OLP) and 13 healthy volunteers were recruited in this study. Real-time quantitative PCR was performed to detect the expressions of RORγτ and FOXP3, which were the lineage-specific transcription factors for Th17 and Treg, respectively. Statistical difference was evaluated by GraphPad Prism 5 software. RESULTS: The results showed that the expressions of RORγτ and FOXP3 in OLP lesions were significantly higher than that in normal oral mucosa, and correlated with the clinical classification of OLP. Additionally, it was found that RORγτ/FOXP3 ratio in atrophic-erosive OLP was significantly higher than that in reticular OLP and control group; Moreover, increased RORγτ/FOXP3 ratio in reticular OLP was found compared with control group, but the difference was not statistically significant. CONCLUSIONS: The results demonstrate that Th17 and Treg cells participate in the immune response in OLP lesions. Th17 predominance of Th17/Treg imbalance may implicate the immune response in atrophic-erosive OLP. These findings help to broaden our view on the pathogenesis of OLP.

Key words: FOXP3, Oral lichen planus, RORγτ, Th17, Treg

中图分类号:

R781.5

谢三祥, 丰琳, 朱声荣, 丁蕾. 转录因子RORγτ和FOXP3在口腔扁平苔藓病损组织中的表达及意义[J]. 上海口腔医学, 2014, 23(4): 472-476.

XIE San-xiang, FENG Lin, ZHU Sheng-rong, DING Lei. Expressions of RORγτ and FOXP3 and clinical significance in patients with oral lichen planus[J]. Shanghai Journal of Stomatology, 2014, 23(4): 472-476.

参考文献

[1] Crincoli V, Di Bisceglie MB, Scivetti M, et al. Oral lichen planus: update on etiopathogenesis, diagnosis and treatment [J]. Immunopharmacol Immunotoxicol, 2011, 33(1): 11-20.
[2] Xie S, Ding L, Xiong Z, et al. Implications of Th1 and Th17 cells in pathogenesis of oral lichen planus [J]. J Huazhong Univ Sci Technolog Med Sci, 2012, 32(3): 451-457.
[3] Haak S, Gyülveszi G, Becher B. Th17 cells in autoimmune disease: changing the verdict [J]. Immunotherapy, 2009, 1(2): 199-203.
[4] Korn T, Bettelli E, Oukka M, et al. IL-17 and Th17 cells [J]. Annu Rev Immunol, 2009, 27: 485-517.
[5] Zheng Y, Valdez PA, Danilenko DM, et al. Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens [J]. Nat Med, 2008, 14(3): 282-289.
[6] Zhang L, Yang XQ, Cheng J, et al. Increased Th17 cells are accompanied by FoxP3(+) Treg cell accumulation and correlated with psoriasis disease severity [J]. Clin Immunol, 2010, 135(1): 108-117.
[7] Walsh LJ, Ishii T, Savage NW, et al. Immunohistologic analysis of epithelial cell populations in oral lichen planus [J]. J Oral Pathol Med, 1990, 19(4): 177-181.
[8] Bag??n-Sebasti??n JV, Mili??n-Masanet MA, Pe?arrocha-Diago M, et al. A clinical study of 205 patients with oral lichen planus [J]. J Oral Maxillofac Surg, 1992, 50(2): 116-118.
[9] Lodi G, Scully C, Carrozzo M, et al. Current controversies in oral lichen planus: report of an international consensus meeting. Part 1. Viral infections and etiopathogenesis [J]. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2005, 100(1): 40-51.
[10] Hemdan NY, Birkenmeier G, Wichmann G, et al. Interleukin-17-producing T helper cells in autoimmunity [J]. Autoimmun Rev, 2010, 9(11): 785-792.
[11] Pène J, Chevalier S, Preisser L, et al. Chronically inflamed human tissues are infiltrated by highly differentiated Th17 lymphocytes [J]. J Immunol, 2008, 180(11): 7423-7430.
[12] Ciprandi G, Filaci G, Battaglia F, et al. Peripheral Th-17 cells in allergic rhinitis: new evidence [J]. Int Immunopharmacol, 2010, 10(2): 226-229.
[13] Sakaguchi S. Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self [J]. Nat Immunol, 2005, 6(4): 345-352.
[14] Tao XA, Xia J, Chen XB, et al. FOXP3 T regulatory cells in lesions of oral lichen planus correlated with disease activity [J]. Oral Dis, 2010, 16(1): 76-82.
[15] Pereira JS, Monteiro BV, Nonaka CF, et al. FoxP3(+) T regulatory cells in oral lichen planus and its correlation with the distinct clinical appearance of the lesions[J]. Int J Exp Pathol,2012,93(4): 287-294.
[16] Paradowska A, Masliniski W, Grzybowska-Kowalczyk A, et al. The function of interleukin 17 in the pathogenesis of rheumatoid arthritis [J]. Arch Immunol Ther Exp (Warsz), 2007, 55(5): 329-334.
[17] Boissier MC, Assier E, Falgarone G, et al. Shifting the imbalance from Th1/Th2 to Th17/treg: the changing rheumatoid arthritis paradigm [J]. Joint Bone Spine, 2008, 75(4): 373-375.
[18] Bettelli E, Carrier Y, Gao W, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells [J]. Nature, 2006, 441(7090): 235-238.
[19] Shao XS, Yang XQ, Zhao XD, et al. The prevalence of Th17 cells and FOXP3 regulate T cells (Treg) in children with primary nephrotic syndrome [J]. Pediatr Nephrol, 2009, 24(9): 1683-1690.