Lamia Ysmail-Dahlouk1, Wafa Nouari1, Mourad Aribi2. 1. Laboratory of Applied Molecular Biology and Immunology, University of Tlemcen, 13000 Tlemcen, Algeria. 2. Laboratory of Applied Molecular Biology and Immunology, University of Tlemcen, 13000 Tlemcen, Algeria. Electronic address: m_aribi@mail.univ-tlemcen.dz.
Abstract
BACKGROUND: Type 1 diabetes (T1D) is associated with an imbalance between inflammation and repair. Recently, the biologically active form of vitamin D3, i.e. 1,25(OH)2D3, 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. METHODS: We examined the effect of 1,25(OH)2D3 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. RESULTS: 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)2D3 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)2D3 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. CONCLUSIONS: 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.
BACKGROUND:Type 1 diabetes (T1D) is associated with an imbalance between inflammation and repair. Recently, the biologically active form of vitamin D3, i.e. 1,25(OH)2D3, 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. METHODS: We examined the effect of 1,25(OH)2D3 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. RESULTS: 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, STAT4tyrosine 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 diabeticpatients than in controls. Treatment with 1,25(OH)2D3 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)2D3 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. CONCLUSIONS: 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.