Oral D-mannose treatment suppresses experimental autoimmune encephalomyelitis via induction of regulatory T cells.
Oral D-mannose treatment suppresses experimental autoimmune encephalomyelitis via induction of regulatory T cells.
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DOI：
10.1016/j.jneuroim.2021.577778
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发表时间：
2022-01-15
影响因子：
3.3
通讯作者：
Ciric B
中科院分区：
文献类型：
--
作者：
Hwang D;Boehm A;Rostami A;Zhang GX;Ciric B
D-甘露糖（D-m）是天然产物中发现的葡萄糖差向异构体，尤其是水果。在糖尿病和气道炎症的小鼠模型中，通过饮用水补充D-m通过改变细胞能量代谢来减轻病理，导致潜在转化生长因子β（TGF-β）的激活，这反过来又诱导了T调节细胞（TCFs）。鉴于TMF在控制实验性自身免疫性脑脊髓炎（EAE）和多发性硬化症（MS）中的神经炎症中很重要，我们假设D-m也可以抑制EAE。我们发现D-m在两种EAE模型中延迟了疾病的发作并降低了疾病的严重程度。重要的是，D-m治疗预防了EAE复发-缓解模型中的复发，该模型模拟了MS的最常见临床表现。EAE抑制伴随着中枢神经系统中CD 4 + FoxP 3 + T细胞的频率增加，表明EAE抑制是由D-m诱导的Treg细胞引起的。这些发现表明，D-m有可能成为MS的安全和低成本的补充疗法。
D-mannose (D-m) is a glucose epimer found in natural products, especially fruits. In mouse models of diabetes and airway inflammation, D-m supplementation via drinking water attenuated pathology by modifying cellular energy metabolism, leading to the activation of latent transforming growth factor beta (TGF-β), which in turn induced T regulatory cells (Tregs). Given that Tregs are important in controlling neuroinflammation in experimental autoimmune encephalomyelitis (EAE) and likely in multiple sclerosis (MS), we hypothesized that D-m could also suppress EAE. We found that D-m delayed disease onset and reduced disease severity in two models of EAE. Importantly, D-m treatment prevented relapses in a relapsing-remitting model of EAE, which mimics the most common clinical manifestation of MS. EAE suppression was accompanied by increased frequency of CD4+FoxP3+ Tregs in the central nervous system, suggesting that EAE suppression resulted from Treg cell induction by D-m. These findings suggest that D-m has the potential to be a safe and low-cost complementary therapy for MS.
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