Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland.
Department of Pediatrics, Endocrinology, Diabetology with Cardiology Division, Medical University of Bialystok, Bialystok, Poland.
Front Immunol. 2022 Aug 24;13:958430. doi: 10.3389/fimmu.2022.958430. eCollection 2022.
Type 1 diabetes (T1D) is autoimmune destruction of the beta cells of pancreatic islets. Due to complexity of that disease, the mechanisms leading to the tolerance breakdown are still not fully understood. Previous hypothesis of imbalance in the Th1 and Th2 cells as the main contributing factor has been recently changed towards role of other lymphocytes - regulatory (Treg) and IL-17A-producing (Th17). Our study aims to assess changes within Treg and Th17 cells in newly diagnosed T1D pediatric patients and their association with disease remission. Flow cytometry implementation allowed for Treg and Th17 analysis in studied groups and further combination with clinical and laboratory data. In addition, expression of diabetes-related genes was tested and evaluated in context of their association with studied lymphocytes. Initial results revealed that Treg and ratio Treg/Th17 are significantly higher in T1D than in healthy controls. Moreover, patients with lower HbA1c and daily insulin requirements demonstrated higher levels of Tregs. Similar tendency for insulin intake was also observed in reference to Th17 cells, together with high levels of these cells in patients demonstrating higher values for c-peptide after 2 years. In low-level Treg patients, that subset correlates with the c-peptide in the admission stage. In addition, higher levels of IL-10 were associated with its correlation with HbA1c and insulin dosage. In the context of gene expression, moderate associations were demonstrated in T1D subjects inter alia between and Treg or ratio Treg/Th17. Cumulatively, our data indicate a possible novel role of Treg and Th17 in mechanism of type 1 diabetes. Moreover, potential prognostic value of these populations has been shown in reference to diabetes remission.
1 型糖尿病(T1D)是胰岛β细胞的自身免疫性破坏。由于该疾病的复杂性,导致耐受破坏的机制仍未完全阐明。先前关于 Th1 和 Th2 细胞失衡是主要致病因素的假说,最近已转变为其他淋巴细胞——调节性(Treg)和 IL-17A 产生(Th17)的作用。我们的研究旨在评估新诊断的 T1D 儿科患者中 Treg 和 Th17 细胞的变化及其与疾病缓解的关系。流式细胞术的实施允许在研究组中分析 Treg 和 Th17,并进一步与临床和实验室数据相结合。此外,还测试和评估了与研究淋巴细胞相关的糖尿病相关基因的表达,并评估了其与研究淋巴细胞的关联。初步结果表明,Treg 和 Treg/Th17 比值在 T1D 患者中明显高于健康对照组。此外,HbA1c 和每日胰岛素需求较低的患者具有更高水平的 Tregs。在 Th17 细胞中也观察到了类似的胰岛素摄入趋势,以及这些细胞水平较高的患者在 2 年后 c 肽值较高。在 Treg 水平较低的患者中,该亚群与入院阶段的 c 肽相关。此外,IL-10 水平升高与 HbA1c 和胰岛素剂量呈正相关。在基因表达方面,T1D 患者中 Treg 或 Treg/Th17 之间表现出中等关联。总之,我们的数据表明 Treg 和 Th17 在 1 型糖尿病发病机制中可能发挥新的作用。此外,这些群体的潜在预后价值已在糖尿病缓解方面得到了证实。