Acta Virol. 2022;66(2):127-138. doi: 10.4149/av_2022_202.
Human T-lymphotropic virus type 1 (HTLV-1) causes chronic infections of human T lymphocytes. The present study aimed to evaluate the effects of 1,25VitD3 on the proportion of Tregs and Th17 cells, the expression of related transcription factors (ROR-γt and FOXP3) and cytokines (IL-10, TGF-β, IL-6, and IL-17 A) in the HTLV-1infected cell lines MT-2 and MT-4. MT-2 and MT-4 cells and control PBMCs were treated with 1,25VitD3 and percentages of Tregs and Th17 cells was determined by flow cytometry. Gene expression and cytokine levels were analyzed by real-time PCR and ELISA, respectively. Treatment with-1,25VitD3 increased the percentage of Tregs in MT-2 and MT-4 cells, while it decreased the percentage of Th17 cells among MT-2 cells. 1,25VitD3 treatment also significantly improved FOXP3 gene expression in MT-2 cells, while reducing ROR-γt-gene expression in MT-2 and MT-4 cells comparing to untreated cells. Treatment with 1,25VitD3 significantly improved IL-10 levels in MT-2 cells, as well as TGF-β levels in both cell lines culture supernatants. 1,25VitD3 treatment diminished IL-6 levels in cell culture supernatants of MT-2 and MT-4 as well as IL-17 A levels in MT-2. Here we showed, that 1,25VitD3 modulated immune responses by enhancing Tregs differentiation and functions as well as inhibiting Th17 differentiation and actions in HTLV-1 infected cell lines. This suggests that VitD3 may have therapeutic effects in HTLV-1-related diseases by suppressing adverse inflammatory responses. Keywords: Tregs; Th17 cells; HTLV-1; 1, 25VitD3.
人 T 淋巴细胞白血病病毒 1 型(HTLV-1)引起人 T 淋巴细胞的慢性感染。本研究旨在评估 1,25VitD3 对 HTLV-1 感染细胞系 MT-2 和 MT-4 中 Tregs 和 Th17 细胞比例、相关转录因子(ROR-γt 和 FOXP3)和细胞因子(IL-10、TGF-β、IL-6 和 IL-17 A)表达的影响。用 1,25VitD3 处理 MT-2 和 MT-4 细胞和对照 PBMCs,并用流式细胞术测定 Tregs 和 Th17 细胞的比例。用实时 PCR 和 ELISA 分别分析基因表达和细胞因子水平。1,25VitD3 处理增加了 MT-2 和 MT-4 细胞中 Tregs 的比例,而降低了 MT-2 细胞中 Th17 细胞的比例。1,25VitD3 处理还显著改善了 MT-2 细胞中 FOXP3 基因的表达,同时降低了未处理细胞中 MT-2 和 MT-4 细胞中 ROR-γt 基因的表达。1,25VitD3 处理显著提高了 MT-2 细胞中 IL-10 的水平,以及两种细胞系培养上清液中 TGF-β 的水平。1,25VitD3 处理降低了 MT-2 和 MT-4 细胞培养上清液中 IL-6 的水平以及 MT-2 细胞中 IL-17 A 的水平。在这里,我们表明,1,25VitD3 通过增强 Tregs 的分化和功能以及抑制 Th17 的分化和作用来调节免疫反应在 HTLV-1 感染的细胞系中。这表明 VitD3 可能通过抑制不良的炎症反应对 HTLV-1 相关疾病具有治疗作用。关键词:Tregs;Th17 细胞;HTLV-1;1,25VitD3。