[1]付丹丹,胡 华,孙 敏,等.Runx3对银屑病患者Th1/Th2细胞平衡的影响及其作用机制[J].新乡医学院学报,2016,33(8):675-679.[doi:10.7683/xxyxyxb.2016.08.007]
 FU Dan-dan,HU Hua,SUN Min,et al.Effect of Runx3 on the balance of Th1/Th2 cells in psoriasis and investigation on its mechanism[J].Journal of Xinxiang Medical University,2016,33(8):675-679.[doi:10.7683/xxyxyxb.2016.08.007]
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Runx3对银屑病患者Th1/Th2细胞平衡的影响及其作用机制
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
33
期数:
2016年8
页码:
675-679
栏目:
临床研究
出版日期:
2016-07-27

文章信息/Info

Title:
Effect of Runx3 on the balance of Th1/Th2 cells in psoriasis and investigation on its mechanism
作者:
付丹丹胡 华孙 敏李占国田中伟
(新乡医学院第一附属医院皮肤性病科,河南 卫辉 453100)
Author(s):
FU Dan-danHU HuaSUN MinLI Zhan-guoTIAN Zhong-wei
(Department of Dermatology,the First Affiliated Hospital of Xinxiang Medical University,Weihui 453100,Henan Province,China)
关键词:
银屑病Runx3CD4+T细胞Th1/Th2细胞平衡RNA干扰GATA3转录因子白细胞介素类干扰素-γ
Keywords:
psoriasisRunx3CD4+T cellTh1/Th2 balanceRNA interferenceGATA3 transcription factorinterleukinsinterferon-γ
分类号:
R758.63
DOI:
10.7683/xxyxyxb.2016.08.007
文献标志码:
A
摘要:
目的 检测Runx3在银屑病患者和健康人外周血CD4+T细胞中转录水平的表达,分析其对Th1/Th2细胞平衡的影响及在银屑病发病中可能的作用机制。方法 选取40例银屑病患者(银屑病组)和35例健康人(健康对照组),应用密度梯度离心法分离其外周血 CD4+T 细胞,采用实时荧光定量聚合酶链反应(qRT-PCR)检测 Runx3转录水平的表达。将体外培养的银屑病患者的CD4+T细胞随机分为空白对照组(未经任何处理组)、阴性对照组(对照siRNA转染组)和Runx3 siRNA组(Runx3 siRNA转染组)。采用Western blot检测沉默效果,流式细胞仪分析Th1、Th2细胞数目,酶联免疫吸附试验检测Th1和Th2细胞相关特异性分泌因子的表达水平,同时采用qRT-PCR和Western blot检测Runx3对Th1/Th2细胞转录因子表达的影响。结果 银屑病组患者CD4+T 细胞Runx3 mRNA的表达水平显著高于健康对照组(P<0.01)。与阴性对照组比较,Runx3 siRNA组银屑病患者CD4+T细胞中Runx3蛋白表达水平下降(P<0.01),同时Th1细胞数目下降(P<0.05),而Th2细胞数目上调(P<0.05),且Th1/Th2细胞比值显著降低(P<0.05);白细胞介素-2(IL-2)、干扰素-γ(IFN-γ)表达水平显著下降(P<0.01),IL-4、IL-10表达水平显著升高(P<0.05);Th1型特异性转录因子T-bet的表达显著降低(0.73±0.06 vs 0.96±0.17)(P<0.01),同时Th2型特异性转录因子GATA3的表达显著升高(1.27±0.11 vs 1.01±0.14)(P<0.05)。结论 Runx3在银屑病患者外周血CD4+T细胞中表达上调,并且可能通过调控Th1/Th2细胞相关特异性转录因子的表达引发Th细胞失衡,从而参与银屑病的病理发病进程。
Abstract:
Objective To analyze the expression of Runx3 in CD4+T cells isolated from normal people and psoriasis patients,as well as its effect and the potential mechanism on the balance of Th1/Th2 cells in the pathological process of psoriasis.Methods Forty patients with psoriasis vulgaris(psoriasis group) and 35 healthy people(healthy control group) were enrolled in the study.The CD4+T cells in peripheral blood were isolated by density gradient centrifugation.The expression level of Runx3 in CD4+T cells was analyzed by quantitative real-time polymerase chain reaction(qRT-PCR).The isolated cells were divided into three groups:blank control group(without any treatment),negative control group (treated with siRNA control transfection) and Runx3 siRNA group (transfected with Runx3 siRNA).The transfection efficiency was evaluated by Western blotting.Flow cytometry was performed to analyze the number of Th1 and Th2 cells.The specific cytokine levels of Th1 and Th2 were detected by enzyme-linked immuno sorbent assay.Furthermore,the effect of Runx3 siRNA on Th1 / Th2 cell transcription factor expression was also explored by qRT-PCR and Western blot.Results Compared with healthy control group,Runx3 protein expression in CD4+T cells in psoriasis group increased significantly(P<0.01).Compared with negative control group,the expression of Runx3 protein in CD4+T cells of psoriasis patients in Runx3 siRNA group decreased significantly,which resulted in the decreasing of the number of Th1 and increasing of the number of Th2,as well as the ratio of Th1/Th2 decreased significantly(P<0.05);moreover,the expressions of interleukin-2(IL-2) and interferon-γ(IFN-γ) decreased significantly while the expressions of IL-4 and IL-10 increased significantly in Runx3 siRNA group(P<0.05);the expression level of Th1-specific transcription factor T-bet decreased significantly while the expression level of Th2-specific transcription factor GATA3 increased significantly in Runx3 siRNA group(P<0.05).Conclusion Runx3 is up-regulated in peripheral blood CD4+T cells from psoriasis patients.Importantly,Runx2 can adjust the imbalance of Th1 / Th2 cells via regulating their specific transcription factors,indicating a critical role in the pathological process of psoriasis.

参考文献/References:

[1] DIANI M,ALTOMARE G,REALI E.T cell responses in psoriasis and psoriatic arthritis[J].Autoimmun Rev,2015,14(4):286-292.
[2] 张平,陈宏翔,段逸群,等.红皮病型银屑病Th1/Th2反应模式的分析[J].华中科技大学学报,2014,34(4):596-601.
[3] CAMPANATI A,ORCIANI M,CONSALES V,et al.Characterization and profiling of immunomodulatory genes in resident mesenchymal stem cells reflect the Th1-Th17/Th2 imbalance of psoriasis[J].Arch Dermatol Res,2014,306(10):915-920.
[4] REIS B S,HOYTEMA VAN KONIJNENBURG D P,GRIVENNIKOV S I,et al.Transcription factor T-bet regulates intraepithelial lymphocyte functional maturation[J].Immunity,2014,41(2):244-256.
[5] DJURETIC I M,LEVANON D,NEGREANU V,et al.Transcription factors T-bet and Runx3 cooperate to activate Ifng and silence Il4 in T helper type 1 cells[J].Nat Immunol,2007,8(2):145-153.
[6] FU D,YU W,LI M,et al.microRNA-138 regulates the balance of Th1/Th2 via targeting RUNX3 in psoriasis[J].Immunol Lett,2015,166(1):55-62.
[7] APEL M,UEBE S,BOWES J,et al.Variants in RUNX3 contribute to susceptibility to psoriatic arthritis,exhibiting further common ground with ankylosing spondylitis[J].Arthritis Rheum,2013,65(5):1224-1231.
[8] HARDEN J L,KRUEGER J G,BOWCOCK A M.The immunogenetics of psoriasis:a comprehensive review[J].J Autoimmun,2015,64:66-73.
[9] DALAL D S,LIN Y C,BRENNAN D M,et al.Quantifying harmful effects of psoriatic diseases on quality of life:cardio-metabolic outcomes in psoriatic arthritis study(COMPASS)[J].Semin Arthritis Rheum,2015,44(6):641-645.
[10] 郑敏,满孝勇.银屑病:希望与挑战[J].中华皮肤科杂志,2016,49(4):731-736.
[11] 魏明,梁颖红,涂玲,等.miRNA-146a 对寻常性银屑病患者外周血CD4+T 细胞的调控研究[J].中华皮肤科杂志,2016,49(4):243-247.
[12] ROH N K,HAN S H,YOUN H J,et al.Tissue and serum inflammatory cytokine levels in korean psoriasis patients:a comparison between plaque and guttate psoriasis[J].Ann Dermatol,2015,27(6):738-743.
[13] AUSTIN L M,OZAWA M,KIKUCHI T,et al.The majority of epidermal T cells in psoriasis vulgaris lesions can produce type 1 cytokineinterferon-gamma,interleukin-2,and tumor necrosis factor-alpha,defining TCL(cytotoxic T lymphocyte) and Th1 effector populations:a type 1 differentiation bias is also measured in circulating blood T cells in psoriatic patients[J].J Invest Dermatol,1999,113(5):752-759.
[14] FU D,SONG X,HU H,et al.Downregulation of RUNX3 moderates the frequency of Th17 and Th22 cells in patients with psoriasis[J].Mol Med Rep,2016,13(6):4606-4612.
[15] NOWYHED H N,HUYNH T R,BLATCHLEY A,et al.The nuclear receptor nr4a1 controls CD8 T cell development through transcriptional suppression of runx3[J].Sci Rep,2015,5:9059.
[16] KOHU K,OHMORI H,WONG W F,et al.The Runx3 transcription factor augments Th1 and down-modulates Th2 phenotypes by interacting with and attenuating GATA3[J].J Immunol,2009,183(12):7817-7824.
[17] BRENNER O,LEVANON D,NEGREANU V,et al.Loss of Runx3 function in leukocytes is associated with spontaneously developed colitis and gastric mucosal hyperplasia[J].Proc Natl Acad Sci USA,2004,101(45):16016-16021.

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更新日期/Last Update: 2016-08-05