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Zinc deficiency drives Th17 polarization and promotes loss of Treg cell function

机译:缺锌驱动Th17极化并促进Treg细胞功能的损失

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A high number of illnesses and disorders are connected to zinc deficiency. Equally, T cell polarization and a balance between different T helper (Th) cell subsets are essential. Therefore, in this study, the influence of zinc deficiency on T cell polarization and on respective signaling pathways was investigated. We uncovered a significantly increased number of regulatory T cells (Treg) and Th17 cells in expanded T cells during zinc deficiency after 3 days of combined treatment with IL-2 and TGF-beta 1 (Treg) or IL-6 and TGF-beta 1 (Th17). No difference in Thl and Th2 cell polarization between zinc-deficient and zinc-adequate status was prominent. On the molecular level, Smad signaling was significantly enhanced by stimulation with TGF-beta 1/IL-6 during zinc deficiency compared to adequate zinc condition. This represents an explanation for the elevated Th17 cell numbers associated with autoimmune disease especially during zinc deficiency. Moreover, Treg cell numbers are increased during zinc deficiency as well. However, those cells might be nonfunctional since a lower expression of miR-146a was uncovered compared to normal zinc concentrations. In summary, an adequate zinc homeostasis is fundamental to slow down or probably stop the progression of autoimmune diseases and infections. Therefore, supplementing zinc might be a therapeutic approach to dampen autoimmune diseases connected to Th17 cells. (C) 2018 Elsevier Inc. All rights reserved.
机译:大量的疾病和疾病与缺锌相关。同样地,T细胞偏振和不同T辅助器(TH)单元子集之间的平衡是必不可少的。因此,研究了研究,研究了锌缺乏对T细胞偏振和相应信号传导途径的影响。在用IL-2和TGF-β1(Treg)或IL-6和TGF-β1(TGF-Beta 1的合并处理后,在锌缺乏症期间,我们发现在缺锌期间在扩增的T细胞中发现了显着增加的调节T细胞(Treg)和Th17细胞。 (th17)。缺锌和锌 - 充分状态之间的THL和TH2细胞极化没有差异突出。在分子水平上,与充足的锌条件相比,在缺锌期间,通过锌缺乏症的刺激显着增强了Smad信号。这代表了与自身免疫疾病相关的升高的TH17细胞数,特别是在缺锌期间。此外,在缺锌期间,Treg细胞数也会增加。然而,由于与正常的锌浓度相比,这些细胞可能是非官能的。总之,足够的锌稳态是放缓或可能阻止自身免疫性疾病和感染的进展的基础。因此,补充锌可能是抑制与Th17细胞的自身免疫疾病的治疗方法。 (c)2018年Elsevier Inc.保留所有权利。

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