玫瑰糠疹患者外周血单个核细胞中转录因子T-bet、GATA-3及Foxp3的mRNA的表达及意义
发布时间：2018-07-23 11:47
【摘要】：目的：玫瑰糠疹(pityriasis rosea, PR)是一种自限性的炎症性皮肤病，病程一般为6-8周。临床特征表现为黄红色,圆形或椭圆形，与皮纹长轴一致的红斑，其表面附有领圈样脱屑，多发生于躯干及四肢近端。玫瑰糠疹病因及发病机制尚不清楚，目前多认为与感染后诱发的细胞免疫失衡有关。 Th1细胞主要介导与细胞毒和局部炎症有关的免疫应答,参与细胞免疫应答，Th2细胞的主要参与体液免疫应答，刺激B细胞分化、增殖,并产生抗体。调节性T细胞(regulatory T cell,Treg)是一群具有免疫抑制和免疫调节功能的细胞,在机体维持免疫自稳、介导体内免疫耐受、以及防止自身免疫性疾病方面具有重要的作用。转录因子T-bet(T box expressed in Tcells)、GATA-3(GATA-binding protein-3)分别正调控Th1细胞、Th2细胞的发育,二者最终决定Th0向Th1/Th2的转化。T-bet在Thl细胞分化中起着核心作用,它不仅控制Thl细胞特征性细胞因子(interferon, IFN)-γ的表达，而且诱导已定向的Th2细胞向相反的Thl细胞分化。GATA-3是Th2特异性转录因子，在转录水平调节Th2类细胞因子的表达，促进Th2细胞特征性细胞因子(interleukin, IL)-4等的产生，限制Th1细胞的分化。Foxp3(forkhead／winged helix transcription factor)特异的表达于调节性T细胞，对Treg细胞的分化以及发挥生物学功能均起着重要的作用。 T-bet、GATA-3及Foxp3在Th细胞的分化中具有重要的作用。T-bet/GATA-3决定Th1/Th2极化分化的关键因素，国内外的学者对T-bet/GATA-3在哮喘、炎症性肠病等多种疾病中表状况做了大量的研究工作。Foxp3介导Treg细胞的分化，大量的研究证实Foxp3与肿瘤、自身免疫性疾病、感染性疾病等有关。在本课题应用实时荧光定量RT-PCR技术检测检测玫瑰糠疹患者在外周血单个核细胞(the peripheral bloodmononuclear cells，PBMC)中转录因子T-bet、GATA-3及Foxp3的mRNA的表达，通过探讨Th1细胞、Th2细胞和Treg细胞分化的关键性转录因子T-bet、GATA-3及Foxp3表达状况，分析其在玫瑰糠疹发病机制中所发挥的作用和意义及该病的免疫功能状态。 方法：病例组;20例玫瑰糠疹患者；对照组：22例健康人群：病例组：均来自河北医科大学第二医院皮肤科门诊，男12例，女8例。平均年龄：23.5岁，病程3天-2月，患者入选标准：⑴均有典型的临床表现(表现黄红色,圆形或椭圆形，与皮纹长轴一致的红斑，其表面附有领圈样脱屑)；⑵受试前临床检查无感染性疾病，无其他免疫相关性疾病，1个月内无系统用药史(未服用免疫抑制剂及激素、抗组胺药)、无不安全性行为史。对照组：22例均无过敏性疾病、自身免疫性疾病及家族史的健康人群，其性别、年龄与病例组经统计学分析，均无统计学差异。本研究采用SYBRGreen I实时荧光定量RT-PCR技术检测病例组与对照组外周血单个核细胞中T-betmRNA、GATA-3mRNA和Foxp3mRNA的表达水平，实验数据应用SPSS13.0统计软件分析，以试验结果应用(x±s)表示，并采用两独立样本比较的t检验，P0.05有统计学意义。 结果：1实验数据显示T-bet mRNA RQ值，玫瑰糠疹组RQ值为0.83±0.57，健康对照组RQ值为0.52±0.36，，经t检验，t值=2.055，P值=0.046，玫瑰糠疹患者组T-bet mRNA表达水平升高，两组间差异有统计学意义(P0.05)。2实验数据显示GATA-3mRNA RQ值，玫瑰糠疹组RQ值为0.68±0.29，健康对照组RQ值为1.22±1.02，经t检验，t值=2.363，P值=0.026，玫瑰糠疹患者组GATA-3mRNA表达水平降低，两组间差异有统计学意义(P0.05)。3实验数据显示Foxp3mRNA RQ，玫瑰糠疹组RQ值为0.92±0.61，健康对照组RQ值为1.48±0.93，经t检验，t值=2.267，P值=0.029，玫瑰糠疹患者组Foxp3mRNA表达水平降低，两组间差异有统计学意义（P0.05）。 结论：玫瑰糠疹患者外周血单个核细胞T-bet mRNA表达水平升高，GATA-3mRNA表达水平降低，可能存在Th1细胞亚群的高表达，Th2细胞亚群的低表达。T-bet/GATA-3mRNA比率升高，Th1/Th2向Th1方向极化。提示玫瑰糠疹的发病过程是以Th1细胞占优势的细胞免疫为主的可能性极大。玫瑰糠疹患者外周血单个核细Foxp3mRNA降低，表明可能存在Treg细胞表达减少，其免疫抑制功能降低。转录因子T-bet、GATA-3、Foxp3均参与了玫瑰糠疹的发病过程。
[Abstract]:Objective: pityriasis rosea (PR) is a self limiting inflammatory dermatosis with a course of 6-8 weeks. The clinical features are yellow red, round or oval, red spots consistent with the long axis of the dermatosis, with a collar like desquamation on the surface, mostly in the trunk and proximal extremities. The etiology and pathogenesis of pityriasis rose is not clear, At present, it is believed that it is related to the imbalance of cellular immunity induced by infection.
Th1 cells mainly mediate immune responses associated with cytotoxic and local inflammation, participate in cellular immune responses, Th2 cells are mainly involved in humoral immune responses, stimulate B cells to differentiate, proliferate, and produce antibodies. Regulatory T cells (regulatory T cell, Treg) are a group of cells with immune suppression and immunomodulatory functions, and are maintained in the body. T-bet (T box expressed in Tcells) and GATA-3 (GATA-binding protein-3) regulate the development of Th1 cells and Th2 cells, respectively. The two of them ultimately determine the transformation of Th0 to play a core role in the differentiation of the cells. It is used not only to control the expression of the characteristic cytokine (interferon, IFN) - gamma of Thl cells, but also to induce the directed Th2 cells to differentiate into the opposite Thl cells, which are Th2 specific transcription factors, regulate the expression of Th2 cell factors at the transcriptional level, and promote the production of Th2 cell specific cytokine (interleukin, IL) -4 and so on. The differentiation of 1 cells (forkhead / winged helix transcription factor) is specifically expressed in the regulatory T cells, which plays an important role in the differentiation of Treg cells and the biological function of Treg cells.
T-bet, GATA-3 and Foxp3 play an important role in the differentiation of Th cells..T-bet/GATA-3 determines the key factors for polarization and differentiation of Th1/Th2. Scholars at home and abroad have done a lot of research on the status of T-bet/GATA-3 in asthma, inflammatory bowel disease and many other diseases,.Foxp3 mediated Treg cell differentiation, and a large number of studies have confirmed Foxp3 and tumor, The application of real time fluorescence quantitative RT-PCR technique to detect the detection and detection of mRNA of T-bet, GATA-3 and Foxp3 in peripheral blood mononuclear cells (the peripheral bloodmononuclear cells, PBMC) in this subject by real time fluorescence quantitative quantitative detection, and to explore the differentiation of Th1 cells, Th2 cells and cells. The expression of key transcription factors, T-bet, GATA-3 and Foxp3, and its role and significance in the pathogenesis of pityriasis rose and the immune function state of the disease.
Methods: case group, 20 cases of rosea pityriasis, control group: 22 healthy people: case group: all from the Department of Dermatology of the second hospital of Hebei Medical University, 12 men and 8 women. The average age is 23.5 years old, the course of disease is -2 months, the standard of admission: (1) all the typical clinical manifestations (rounded, round or oval, and skin length) Uninfected diseases, no other immune related diseases, no systematic history of drug use within 1 months (not taking immunosuppressive agents and hormones, antihistamines) and a history of safe behavior without any other immune related diseases. In the control group, 22 cases had no allergic diseases, autoimmune diseases and families. In the healthy population of history, there was no statistical difference between the sex, age and case group. The SYBRGreen I real-time fluorescence quantitative RT-PCR technique was used to detect the expression level of T-betmRNA, GATA-3mRNA and Foxp3mRNA in the peripheral blood mononuclear cells of the case group and the control group. The experimental data were analyzed by the SPSS13.0 statistical software. The results of the test were applied (x + s) and the t test of two independent samples was used. P0.05 had statistical significance.
Results: 1 the experimental data showed the value of T-bet mRNA RQ, the RQ value of the rosea pityriasis group was 0.83 + 0.57, the RQ value of the healthy control group was 0.52 + 0.36, the t test, t value =2.055, P =0.046, the T-bet mRNA expression level of the patients with pityriasis rose, the difference between the two groups was statistically significant, and the value of the rosea pityriasis group was 0.6. 8 + 0.29, the RQ value of the healthy control group was 1.22 + 1.02, t test, t value =2.363, P value =0.026, the GATA-3mRNA expression level in the patients with pityriasis rose, and the difference between the two groups was statistically significant (P0.05).3 experimental data showed Foxp3mRNA RQ, the RQ value of the rosea pityriasis group was 0.92 + 0.61, and the healthy Kang control group was 1.48 + 0.93. The expression level of Foxp3mRNA in patients with pityriasis rosea decreased, and the difference between the two groups was statistically significant (P0.05).
Conclusion: the expression level of T-bet mRNA in peripheral blood mononuclear cells of the patients with furfuronyriasis rose, the expression level of GATA-3mRNA decreased, the high expression of Th1 cell subsets may exist, the low expression of.T-bet/GATA-3mRNA in Th2 cell subsets increased and Th1/Th2 was polarized to Th1, suggesting that the pathogenesis of the rash is the dominant cells in Th1 cells. The possibility of immunization was great. The peripheral blood mononuclear Foxp3mRNA of the patients with pityriasis rose decreased, suggesting that the expression of Treg cells may be reduced and its immunosuppressive function decreased. The transcription factor T-bet, GATA-3, and Foxp3 were all involved in the pathogenesis of pityriasis rosea.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R758.64
本文编号：2139315
[Abstract]:Objective: pityriasis rosea (PR) is a self limiting inflammatory dermatosis with a course of 6-8 weeks. The clinical features are yellow red, round or oval, red spots consistent with the long axis of the dermatosis, with a collar like desquamation on the surface, mostly in the trunk and proximal extremities. The etiology and pathogenesis of pityriasis rose is not clear, At present, it is believed that it is related to the imbalance of cellular immunity induced by infection.
Th1 cells mainly mediate immune responses associated with cytotoxic and local inflammation, participate in cellular immune responses, Th2 cells are mainly involved in humoral immune responses, stimulate B cells to differentiate, proliferate, and produce antibodies. Regulatory T cells (regulatory T cell, Treg) are a group of cells with immune suppression and immunomodulatory functions, and are maintained in the body. T-bet (T box expressed in Tcells) and GATA-3 (GATA-binding protein-3) regulate the development of Th1 cells and Th2 cells, respectively. The two of them ultimately determine the transformation of Th0 to play a core role in the differentiation of the cells. It is used not only to control the expression of the characteristic cytokine (interferon, IFN) - gamma of Thl cells, but also to induce the directed Th2 cells to differentiate into the opposite Thl cells, which are Th2 specific transcription factors, regulate the expression of Th2 cell factors at the transcriptional level, and promote the production of Th2 cell specific cytokine (interleukin, IL) -4 and so on. The differentiation of 1 cells (forkhead / winged helix transcription factor) is specifically expressed in the regulatory T cells, which plays an important role in the differentiation of Treg cells and the biological function of Treg cells.
T-bet, GATA-3 and Foxp3 play an important role in the differentiation of Th cells..T-bet/GATA-3 determines the key factors for polarization and differentiation of Th1/Th2. Scholars at home and abroad have done a lot of research on the status of T-bet/GATA-3 in asthma, inflammatory bowel disease and many other diseases,.Foxp3 mediated Treg cell differentiation, and a large number of studies have confirmed Foxp3 and tumor, The application of real time fluorescence quantitative RT-PCR technique to detect the detection and detection of mRNA of T-bet, GATA-3 and Foxp3 in peripheral blood mononuclear cells (the peripheral bloodmononuclear cells, PBMC) in this subject by real time fluorescence quantitative quantitative detection, and to explore the differentiation of Th1 cells, Th2 cells and cells. The expression of key transcription factors, T-bet, GATA-3 and Foxp3, and its role and significance in the pathogenesis of pityriasis rose and the immune function state of the disease.
Methods: case group, 20 cases of rosea pityriasis, control group: 22 healthy people: case group: all from the Department of Dermatology of the second hospital of Hebei Medical University, 12 men and 8 women. The average age is 23.5 years old, the course of disease is -2 months, the standard of admission: (1) all the typical clinical manifestations (rounded, round or oval, and skin length) Uninfected diseases, no other immune related diseases, no systematic history of drug use within 1 months (not taking immunosuppressive agents and hormones, antihistamines) and a history of safe behavior without any other immune related diseases. In the control group, 22 cases had no allergic diseases, autoimmune diseases and families. In the healthy population of history, there was no statistical difference between the sex, age and case group. The SYBRGreen I real-time fluorescence quantitative RT-PCR technique was used to detect the expression level of T-betmRNA, GATA-3mRNA and Foxp3mRNA in the peripheral blood mononuclear cells of the case group and the control group. The experimental data were analyzed by the SPSS13.0 statistical software. The results of the test were applied (x + s) and the t test of two independent samples was used. P0.05 had statistical significance.
Results: 1 the experimental data showed the value of T-bet mRNA RQ, the RQ value of the rosea pityriasis group was 0.83 + 0.57, the RQ value of the healthy control group was 0.52 + 0.36, the t test, t value =2.055, P =0.046, the T-bet mRNA expression level of the patients with pityriasis rose, the difference between the two groups was statistically significant, and the value of the rosea pityriasis group was 0.6. 8 + 0.29, the RQ value of the healthy control group was 1.22 + 1.02, t test, t value =2.363, P value =0.026, the GATA-3mRNA expression level in the patients with pityriasis rose, and the difference between the two groups was statistically significant (P0.05).3 experimental data showed Foxp3mRNA RQ, the RQ value of the rosea pityriasis group was 0.92 + 0.61, and the healthy Kang control group was 1.48 + 0.93. The expression level of Foxp3mRNA in patients with pityriasis rosea decreased, and the difference between the two groups was statistically significant (P0.05).
Conclusion: the expression level of T-bet mRNA in peripheral blood mononuclear cells of the patients with furfuronyriasis rose, the expression level of GATA-3mRNA decreased, the high expression of Th1 cell subsets may exist, the low expression of.T-bet/GATA-3mRNA in Th2 cell subsets increased and Th1/Th2 was polarized to Th1, suggesting that the pathogenesis of the rash is the dominant cells in Th1 cells. The possibility of immunization was great. The peripheral blood mononuclear Foxp3mRNA of the patients with pityriasis rose decreased, suggesting that the expression of Treg cells may be reduced and its immunosuppressive function decreased. The transcription factor T-bet, GATA-3, and Foxp3 were all involved in the pathogenesis of pityriasis rosea.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R758.64
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