School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands.
PLoS One. 2009 Aug 13;4(8):e6635. doi: 10.1371/journal.pone.0006635.
In several autoimmune diseases, including multiple sclerosis (MS), a compromised regulatory T cell (Treg) function is believed to be critically involved in the disease process. In vitro, the biologically active metabolite of vitamin D has been shown to promote Treg development. A poor vitamin D status has been linked with MS incidence and MS disease activity. In the present study, we assess a potential in vivo correlation between vitamin D status and Treg function in relapsing remitting MS (RRMS) patients.
METHODOLOGY/PRINCIPAL FINDINGS: Serum levels of 25-hydroxyvitamin D (25(OH)D) were measured in 29 RRMS patients. The number of circulating Tregs was assessed by flow-cytometry, and their functionality was tested in vitro in a CFSE-based proliferation suppression assay. Additionally, the intracellular cytokine profile of T helper cells was determined directly ex-vivo by flow-cytometry. Serum levels of 25(OH)D correlated positively with the ability of Tregs to suppress T cell proliferation (R = 0.590, P = 0.002). No correlation between 25(OH)D levels and the number of Tregs was found. The IFN-gamma/IL-4 ratio (Th1/Th2-balance) was more directed towards IL-4 in patients with favourable 25(OH)D levels (R = -0.435, P = 0.023).
CONCLUSIONS/SIGNIFICANCE: These results show an association of high 25(OH)D levels with an improved Treg function, and with skewing of the Th1/Th2 balance towards Th2. These findings suggest that vitamin D is an important promoter of T cell regulation in vivo in MS patients. It is tempting to speculate that our results may not only hold for MS, but also for other autoimmune diseases. Future intervention studies will show whether modulation of vitamin D status results in modulation of the T cell response and subsequent amelioration of disease activity.
在包括多发性硬化症（MS）在内的几种自身免疫性疾病中，调节性 T 细胞（Treg）功能受损被认为与疾病过程密切相关。在体外，维生素 D 的生物活性代谢物已被证明可促进 Treg 的发育。维生素 D 状态不佳与 MS 的发病率和 MS 疾病活动度有关。在本研究中，我们评估了复发缓解型 MS（RRMS）患者中维生素 D 状态与 Treg 功能之间的潜在体内相关性。
方法/主要发现：在 29 名 RRMS 患者中测量了血清 25-羟维生素 D（25（OH）D）水平。通过流式细胞术评估循环 Treg 的数量，并通过 CFSE 增殖抑制试验在体外测试其功能。此外，通过流式细胞术直接在体外测定 T 辅助细胞的细胞内细胞因子谱。血清 25（OH）D 水平与 Treg 抑制 T 细胞增殖的能力呈正相关（R = 0.590，P = 0.002）。未发现 25（OH）D 水平与 Treg 数量之间存在相关性。在 25（OH）D 水平有利的患者中，IFN-γ/IL-4 比值（Th1/Th2 平衡）更偏向于 IL-4（R = -0.435，P = 0.023）。
结论/意义：这些结果表明，高 25（OH）D 水平与 Treg 功能的改善以及 Th1/Th2 平衡向 Th2 的倾斜有关。这些发现表明，维生素 D 是 MS 患者体内 T 细胞调节的重要促进剂。推测我们的结果不仅适用于 MS，也适用于其他自身免疫性疾病。未来的干预研究将表明，维生素 D 状态的调节是否会导致 T 细胞反应的调节以及随后疾病活动度的改善。
