Ysmail-Dahlouk Lamia, Nouari Wafa, Aribi Mourad
Laboratory of Applied Molecular Biology and Immunology, University of Tlemcen, 13000 Tlemcen, Algeria.
Laboratory of Applied Molecular Biology and Immunology, University of Tlemcen, 13000 Tlemcen, Algeria.
Immunol Lett. 2016 Nov;179:122-130. doi: 10.1016/j.imlet.2016.10.002. Epub 2016 Oct 4.
Type 1 diabetes (T1D) is associated with an imbalance between inflammation and repair. Recently, the biologically active form of vitamin D, i.e. 1,25(OH)D, has been reported to have potent immunomodulatory effects on both innate and adaptive immune cells, as well as on the production of their specific cytokines.
We examined the effect of 1,25(OH)D on the production of proinflammatory Th1/Th17 and anti-inflammatory Th2/Treg related cytokines, as well as on the phosphorylation of monocyte-expressed STAT4 and STAT6 at the recent-onset human T1D.
The levels of IFN-γ, IL-17 and nitric oxide (NO) production were significantly increased in peripheral blood mononuclear cells (PBMCs) from patients with T1D compared to controls. Similarly, STAT4 tyrosine phosphorylation (p-STAT4, Tyr693) levels were significantly increased in monocytes from patients when compared to controls. Conversely, the levels of IL-4, IL-10 and p-STAT6 (Tyr641) were significantly decreased in type 1 diabetic patients than in controls. Treatment with 1,25(OH)D resulted in significant up-regulation of IL-4, IL-10, arginase activity, and p-STAT6 and, conversely, down-regulation of IFN-γ, IL-17 and NO production levels, as well as p-STAT4. Additionally, 1,25(OH)D significantly enhanced Treg-to-Th17 ratio, and induced a significant decrease in Th1-to-Th2, NO production-to-arginase activity and p-STAT4-to-p-STAT6 ratios.
Our study suggests that the biologically active form of vitamin D can reverse the activation of inflammatory pathways at the onset of T1D. Additionally, its immunomodulation properties may vary depending on the overall patterns of cytokines. From a therapeutic point of view, vitamin D may potentially be suggested as an immunological adjuvant and a potential anti-inflammatory agent in individuals at risk of T1D.
1型糖尿病（T1D）与炎症和修复之间的失衡有关。最近，有报道称维生素D的生物活性形式，即1,25(OH)D，对先天性和适应性免疫细胞及其特定细胞因子的产生具有强大的免疫调节作用。
我们研究了1,25(OH)D对近期发病的人类T1D患者促炎Th1/Th17和抗炎Th2/Treg相关细胞因子产生的影响，以及对单核细胞表达的STAT4和STAT6磷酸化的影响。
与对照组相比，T1D患者外周血单个核细胞（PBMC）中IFN-γ、IL-17和一氧化氮（NO）的产生水平显著升高。同样，与对照组相比，患者单核细胞中STAT4酪氨酸磷酸化（p-STAT4，Tyr693）水平显著升高。相反，1型糖尿病患者的IL-4、IL-10和p-STAT6（Tyr641）水平明显低于对照组。用1,25(OH)D治疗导致IL-4、IL-10、精氨酸酶活性和p-STAT6显著上调，相反，IFN-γ、IL-17和NO产生水平以及p-STAT4下调。此外，1,25(OH)D显著提高了Treg与Th17的比例，并导致Th1与Th2、NO产生与精氨酸酶活性以及p-STAT4与p-STAT6的比例显著降低。
我们的研究表明，维生素D的生物活性形式可以在T1D发病时逆转炎症途径的激活。此外，其免疫调节特性可能因细胞因子的整体模式而异。从治疗角度来看，维生素D可能被建议作为T1D高危个体的免疫佐剂和潜在的抗炎剂。
