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DIM mitigates the development of experimental autoimmune encephalomyelitis by maintaining the stability and suppressive function of regulatory T cells
Cellular Immunology ( IF 3.7 ) Pub Date : 2020-10-17 , DOI: 10.1016/j.cellimm.2020.104238
Sujuan Yang , Lixi Tan , Yingying Chen , Aiqun Liu , Mingfan Hong , Zhongxing Peng

Recent studies have revealed that indoles, dietary ligands of the aryl hydrocarbon receptor (AhR), have immunomodulatory characteristics of balancing the differentiation of regulatory T cells (Tregs) and Th17 cells in multiple autoimmune diseases.

In this study, we aimed to investigate the potency of the indole, 3,3′-diindolylmethane (DIM), on the stability and suppressive function of Tregs in experimental autoimmune encephalomyelitis (EAE). Furthermore, we used the AhR antagonist CH223191 to verify that DIM exerts its effects on Tregs through the activation of AhR.

We found that DIM treatment significantly alleviated the severity of EAE by maintaining the stability and suppressive function of Tregs instead of facilitating the differentiation of Tregs. Thus, these DIM-treated Tregs might indirectly inhibit the generation of Th17 cells and the production of proinflammatory cytokines. And we confirmed the critical role of AhR in the EAE model.

Our study further investigated the mechanisms by which dietary indoles promote Treg activity in the EAE model. DIM may act as a novel therapeutic to restrain autoimmune inflammation in multiple sclerosis.



中文翻译:

DIM通过维持调节性T细胞的稳定性和抑制功能来减轻实验性自身免疫性脑脊髓炎的发展

最近的研究表明,吲哚是芳烃受体(AhR)的饮食配体,在多种自身免疫性疾病中具有平衡调节性T细胞(Tregs)和Th17细胞分化的免疫调节特性。

在这项研究中,我们旨在调查吲哚3,3'-二吲哚基甲烷(DIM)对Treg在实验性自身免疫性脑脊髓炎(EAE)中的稳定性和抑制功能的作用。此外,我们使用了AhR拮抗剂CH223191来验证DIM通过激活AhR对Treg发挥作用。

我们发现,DIM治疗通过维持Tregs的稳定性和抑制功能,而不是促进Tregs的分化,大大减轻了EAE的严重性。因此,这些经DIM处理的Tregs可能间接抑制Th17细胞的产生和促炎细胞因子的产生。我们证实了AhR在EAE模型中的关键作用。

我们的研究进一步调查了饮食吲哚在EAE模型中促进Treg活性的机制。DIM可以作为抑制多发性硬化症中自身免疫炎症的新型疗法。

更新日期:2020-10-30
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