University Cell Immunotherapy Centre, Masaryk University, Brno, Czech Republic; Laboratory of Molecular Pathology, Medical Faculty, Palacky University, Olomouc, Czech Republic.
Cell Immunol. 2010;260(2):70-4. doi: 10.1016/j.cellimm.2009.10.012.
Regulatory T cells (Tregs) are critical regulators of autoimmune diseases, including type 1 diabetes mellitus. It is hypothesised that Tregs' function can be influenced by changes in the expression of specific microRNAs (miRNAs). Thus, we performed miRNAs profiling in a population of Tregs separated from peripheral blood of five type 1 diabetic patients and six healthy donors. For more detailed molecular characterisation of Tregs, we additionally compared miRNAs expression profiles of Tregs and conventional T cells. Tregs were isolated according to CD3+, CD4+, CD25(hi)+ and CD127- by flow cytometry, and miRNA expression profiling was performed using TaqMan Array Human MicroRNA Panel-1 (384-well low density array). In Tregs of diabetic patients we found significantly increased expression of miRNA-510 (p=0.05) and decreased expression of both miRNA-342 (p<0.0001) and miRNA-191 (p=0.0079). When comparing Tregs and T cells, we revealed that Tregs had significant higher expression of miRNA-146a and lower expression of eight specific miRNAs (20b, 31, 99a, 100, 125b, 151, 335, and 365). To our knowledge, this is the first study demonstrating changes in miRNA expression profiles occurring in Tregs of T1D patients and a miRNAs signature of adult Tregs.
调节性 T 细胞(Tregs)是自身免疫性疾病(包括 1 型糖尿病)的关键调节因子。据推测,Tregs 的功能可能受到特定 microRNA(miRNA)表达变化的影响。因此,我们对 5 例 1 型糖尿病患者和 6 名健康供体外周血分离的 Tregs 进行了 miRNA 谱分析。为了更详细地对 Tregs 进行分子特征分析,我们还比较了 Tregs 和常规 T 细胞的 miRNA 表达谱。Tregs 通过流式细胞术根据 CD3+、CD4+、CD25(hi)+和 CD127-进行分离,并使用 TaqMan Array Human MicroRNA Panel-1(384 孔低密度阵列)进行 miRNA 表达谱分析。我们发现,在糖尿病患者的 Tregs 中,miRNA-510 的表达显著增加(p=0.05),miRNA-342 和 miRNA-191 的表达显著降低(p<0.0001 和 p=0.0079)。当比较 Tregs 和 T 细胞时,我们发现 Tregs 中 miRNA-146a 的表达显著升高,而 8 种特定 miRNA(20b、31、99a、100、125b、151、335 和 365)的表达显著降低。据我们所知,这是首次证明 T1D 患者 Tregs 中发生的 miRNA 表达谱变化和成人 Tregs 的 miRNA 特征的研究。