Transcriptional characteristics of CD4 T cells in young asthmatic children: RORC and FOXP3 axis.
Transcriptional characteristics of CD4 T cells in young asthmatic children: RORC and FOXP3 axis.
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DOI：
10.2147/jir.s25314
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发表时间：
2011
影响因子：
4.5
通讯作者：
Hamzaoui K
中科院分区：
文献类型：
--
作者：
Hamzaoui A;Maalmi H;Berraïes A;Abid H;Ammar J;Hamzaoui K
哮喘是一种慢性炎症性疾病，假设是由自身反应性Th2细胞引起的，而Th1和调节性T细胞可能提供保护。Th亚群的发育依赖于谱系特异性转录因子的表达。本研究旨在评估哮喘儿童外周血中CD4+T细胞亚群的平衡状态。检测30例哮喘患儿(轻度哮喘18例，中度哮喘12例)外周血单个核细胞(PBMC)mRNA的表达。实时定量聚合酶链式反应(RT-PCR)检测Tbx21、GATA-3、RORC、FOXP3和EBI3mRNA的表达。采用流式细胞术检测哮喘患儿外周血中IL-2、IL-4、IL-10和干扰素-γ的表达。采用酶联免疫吸附试验检测血清IL-6、IL-17细胞因子水平。CD4+和CD8+T细胞产生IL-4、IL-6和IL-17的百分比显著增加。哮喘儿童CD_4~+细胞产生干扰素-γ的百分率降低。哮喘患者外周血中GATA-3(Th2)、视黄醇相关孤儿受体C(RORC)(Th17)和EBI3的表达均高于正常对照组。哮喘儿童FoxP3(Treg)和Tbx21(Th1)表达降低(P<；0.0001和P<；0.0001)。转录因子比值分析显示哮喘患者RORC/FOXP3升高(P=0.0001)，Tbx21/GATA-3比值显著降低(P=0.0001)。青少年哮喘患者的特点是IL-4产生增加，干扰素-γ合成减少。血清IL-17和IL-6水平的升高支持了年轻哮喘患者的炎症环境。结果表明，FOXP3和RORC基因的表达可能与Treg细胞免疫耐受低下所介导的持续性炎症过程有关。哮喘患者Tbx21/GATA-3和RORC/FOXP3比例失调与Th1、Th17和Treg细胞在炎症过程中存在可塑性一致。
Asthma is a chronic inflammatory disorder, hypothetically caused by autoreactive Th2 cells, whereas Th1 and regulatory T cells may confer protection. The development of Th subpopulations is dependent on the expression of lineage-specific transcription factors. This study aimed to assess the balance of CD4+ T cell populations in asthmatic children. Peripheral blood mononuclear cells (PBMC) mRNA expression was assessed in 30 asthmatic children (18 patients with mild asthma and 12 with moderate asthma). Real-time polymerase chain reaction (RT-PCR) quantified TBX21, GATA-3, RORC, FOXP3, and EBI3 mRNA expression. Intracellular cytokine expression of IL-2, IL-4, IL-10, and IFN-γ in CD4+ T cells in asthmatic children was measured by flow cytometry. IL-6 and IL-17 cytokines were assessed in serum by enzyme-linked immunosorbent assay (ELISA). A significant increase was found in the percentage of CD4+ and CD8+ T cell-producing IL-4, IL-6, and IL-17. A decreased percentage of CD4+ producing IFN-γ in asthmatic children was found. Expression of GATA-3 (Th2), retinoid-related orphan receptor C (RORC) (Th17), and EBI3 were increased in asthmatic patients compared to healthy controls. Expression of FOXP3 (Treg) and TBX21 (Th1) were decreased (P < 0.0001 and P < 0.0001) in asthmatic children. Analysis of transcription factor ratios revealed an increase in the RORC/FOXP3 (P = 0.0001), and a significant decrease of TBX21/GATA-3 (P = 0.0001) ratios in patients with asthma. Young asthmatics were characterized by increased IL-4 production and low IFN-γ synthesis. The increased serum IL-17 and IL-6 levels sustained an inflammatory environment in young asthmatics. The results indicate that FOXP3 and RORC mRNA expression could be associated with the sustained inflammatory process, transduced by low immune tolerance by Treg cells. The TBX21/GATA-3 and RORC/FOXP3 ratios dysregulation in asthmatics is consistent with the plasticity existing between Th1, Th17, and Treg cells during inflammation.