Ozgur Burcin Aydin, Cinar Suzan Adin, Coskunpinar Ender, Yilmaz Abdullah, Altunkanat Derya, Deniz Gunnur, Gurol Ali Osman, Yilmaz M Temel
Department of Medical Biology and Genetics, Faculty of Medicine, Demiroglu Bilim University, Istanbul, Turkey.
Diabetes Application and Research Center, Demiroglu Bilim University, Istanbul, Turkey.
Immunol Res. 2023 Jun;71(3):451-462. doi: 10.1007/s12026-022-09355-z. Epub 2023 Jan 3.
Th cells play an important role in pathogenesis of type 1 diabetes (T1D). Peripheral blood mononuclear cells were isolated from peripheral blood samples from newly diagnosed (ND), 1-year (1YD), and 5-year T1D (5YD) patients (n:8 of each group), 8 healthy controls (HC), and cultured for 24 h under unstimulated (US) and stimulated conditions. Cell ratios of Th1, Th2, Th17, Treg, and intracellular levels of IFN-γ, TNF-α, IL-10, TGF-β, IL-5, IL-13, IL-17, and IL-21 cytokines were evaluated using the flow cytometry. mRNA expressions of transcription factors T-bet, GATA3, ROR-γt, and FOXP3 of these cells were determined by real-time PCR. Reduced CD4CD25 cell ratios were detected in ND. CD4CD25 cells were found to be reduced in ND and 1YD compared to HC under IL-2-stimulated conditions. Intracellular IFN-γ and TNF-α levels were low in all patients under US and IL-12-stimulated conditions. IL-17A and IL-21 were found to be high in patients with IL-6-stimulated conditions. Expressions of IL-10 and TGF-β have been observed to be reduced in patients. Th1/Th2, Th17/Treg, and Th1/Treg ratios were higher in patient groups. FOXP3 and GATA3 mRNA expressions were found to be low in patients, while RORγt and T-bet mRNA levels were higher than HC. Th1, Th17, and Treg cells and their cytokines have been shown to be associated with type 1 diabetes.
辅助性T细胞（Th细胞）在1型糖尿病（T1D）的发病机制中起重要作用。从新诊断的（ND）、患病1年的（1YD）和患病5年的T1D（5YD）患者（每组n = 8）、8名健康对照者（HC）的外周血样本中分离外周血单个核细胞，并在未刺激（US）和刺激条件下培养24小时。使用流式细胞术评估Th1、Th2、Th17、调节性T细胞（Treg）的细胞比例以及细胞内γ干扰素（IFN-γ）、肿瘤坏死因子-α（TNF-α）、白细胞介素-10（IL-10）、转化生长因子-β（TGF-β）、IL-5、IL-13、IL-17和IL-21细胞因子的水平。通过实时聚合酶链反应（PCR）测定这些细胞中转录因子T-bet、GATA3、维甲酸相关孤儿受体-γt（ROR-γt）和叉头框蛋白P3（FOXP3）的信使核糖核酸（mRNA）表达。在新诊断患者中检测到CD4CD25细胞比例降低。在白细胞介素-2（IL-2）刺激条件下，与健康对照者相比，新诊断患者和患病1年患者的CD4CD25细胞减少。在未刺激和IL-12刺激条件下，所有患者的细胞内IFN-γ和TNF-α水平均较低。在IL-6刺激条件下，患者的IL-17A和IL-21水平较高。已观察到患者中IL-10和TGF-β的表达降低。患者组中Th1/Th2、Th17/Treg和Th1/Treg比例较高。发现患者中FOXP3和GATA3的mRNA表达较低，而RORγt和T-bet的mRNA水平高于健康对照者。Th1、Th17和Treg细胞及其细胞因子已被证明与1型糖尿病有关。
