Haghmorad Dariush, Yazdanpanah Esmaeil, Jadid Tavaf Maryam, Zargarani Simin, Soltanmohammadi Azita, Mahmoudi Mohammad Bagher, Mahmoudi Mahmoud
Department of Pathology and Laboratory Medicine, School of Medicine, Semnan University of Medical Sciences , Semnan , Iran.
Department of Immunology, School of Medicine, Semnan University of Medical Sciences , Semnan , Iran.
Neurol Res. 2019 Oct;41(10):943-957. doi: 10.1080/01616412.2019.1650218. Epub 2019 Aug 12.
Multiple sclerosis (MS) is a complex inflammatory and demyelinating disease of the central nervous system (CNS) frequently starts in young adulthood. Demyelination, inflammatory and axonal damage in the CNS is the pathological hallmark of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. 1, 25-dihydroxyvitamin D (Vitamin D) is involved in calcium regulation, phosphorus homeostasis, and bone mineralization. In addition, vitamin D has potential inhibitory effects on immune cells in various inflammatory and autoimmunity disease. C57BL/6 female mice were divided into prevention groups (low, middle and high doses) and treatment groups (middle and high doses). Prevention groups received vitamin D 2 weeks before EAE induction, and treatment groups were treated with vitamin D simultaneous with EAE induction. Vitamin D inhibits the development of EAE in a dose-dependent manner. Histological studies revealed reduced demyelination and limited infiltration into CNS, moreover vitamin D increased the production of IL-4, IL-10, and TGF-β, while a significant reduction in the production of IFN-γ, IL-6, TNF-α, and IL-17 was observed. Flow cytometry results for CD4 T cell subsets in compliance with ELISA cytokine assay results showed a significant decrease in the percentage of Th1 and Th17, but also a significant increase in the percentage of Th2 and Treg for middle and high dose vitamin D treated mice. Real-time PCR results indicated that middle and high dose vitamin D treatment reduced T-bet and ROR-γt expression, but enhanced GATA3 and Foxp3 expression. Real-Time PCR results in CNS for T cell subsets related cytokines and transcription factors supported the results of flow cytometry and ELISA. This study indicated that middle and high doses of vitamin D3 deviate the balance between Th1/Th2 and Th17/Treg to Th2 and Treg. Moreover, vitamin D3 could reduce the incidence and severity of EAE clinical disease.
多发性硬化症（MS）是一种中枢神经系统（CNS）的复杂炎症性脱髓鞘疾病，常始于年轻成年期。中枢神经系统的脱髓鞘、炎症和轴突损伤是实验性自身免疫性脑脊髓炎（EAE）的病理标志，EAE是多发性硬化症的一种动物模型。1,25 - 二羟基维生素D（维生素D）参与钙调节、磷稳态和骨矿化。此外，维生素D对各种炎症和自身免疫性疾病中的免疫细胞具有潜在抑制作用。将C57BL/6雌性小鼠分为预防组（低、中、高剂量）和治疗组（中、高剂量）。预防组在诱导EAE前2周接受维生素D，治疗组在诱导EAE的同时接受维生素D治疗。维生素D以剂量依赖性方式抑制EAE的发展。组织学研究显示脱髓鞘减少且中枢神经系统浸润受限，此外维生素D增加了IL - 4、IL - 10和TGF -β的产生，同时观察到IFN -γ、IL - 6、TNF -α和IL - 17的产生显著减少。与ELISA细胞因子检测结果一致的CD4 T细胞亚群流式细胞术结果显示，中、高剂量维生素D处理的小鼠中Th1和Th17的百分比显著降低，但Th2和Treg的百分比也显著增加。实时PCR结果表明，中、高剂量维生素D处理降低了T - bet和ROR -γt的表达，但增强了GATA3和Foxp3的表达。中枢神经系统中T细胞亚群相关细胞因子和转录因子的实时PCR结果支持了流式细胞术和ELISA的结果。本研究表明，中、高剂量的维生素D3使Th1/Th2和Th17/Treg之间的平衡偏向Th2和Treg。此外，维生素D3可降低EAE临床疾病的发病率和严重程度。
