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亚硒酸钠体外可抑制调节性 T 细胞分化。

Sodium Selenite Diminished the Regulatory T Cell Differentiation In Vitro.

机构信息

Laboratory of Immunology and Cellular and Molecular Biology, Faculty of Chemical Sciences, Autonomous University of San Luis Potosí, UASLP, San Luis Potosí, Mexico.

Unidad de Investigación Biomédica, Delegación Zacatecas, Instituto Mexicano del Seguro Social, IMSS, Interior de la Alameda No.45, 98000, Zacatecas, Zac, México.

出版信息

Biol Trace Elem Res. 2023 Apr;201(4):1559-1566. doi: 10.1007/s12011-022-03263-x. Epub 2022 Apr 29.

DOI:10.1007/s12011-022-03263-x
PMID:35486317
Abstract

Sodium selenite modulates the activity of lymphocytes. It negatively regulates the suppressive activity of cells and increases the immune response. In this study, we evaluated whether the regulatory T cell differentiation was modulated by sodium selenite. The percentages of CD4+CD25+Foxp3+, CD4+CD25+, and CD4+CTLA-4+ cells in CD4+ T cells cultures stimulated with IL-2 and TGF-β in the presence or absence of selenium, in the form of sodium selenite (2.0×10M), were evaluated by flow cytometry. The mRNA expression of TET2/3 enzymes and IL-10 was analyzed by RT-qPCR and the levels of IL-10 were measured by an ELISA. We observed a decrease in CD4+CD25+Foxp3+ and CD4+CTLA-4+ cells in presence of selenium. However, normal percentages were reached again after selenium removal. An increase in CD4+CTL4-4+ cells was detected in selenium-primed cell cultures in absence of IL-2 and TGF-β. In addition, we observed a decrease in TET3 in presence of selenium. Finally, we observed an augment in IL-10 transcription and protein levels and relative expression of TET2 in cultures exposed to selenium. We suggest that selenium reversibly affects the regulatory T cell differentiation in vitro. Likewise, selenium may modulate Treg percentages promoting optimal immune responses and, at the same time, the expression of specific suppressor molecules.

摘要

亚硒酸钠调节淋巴细胞的活性。它负调控细胞的抑制活性,增加免疫反应。在本研究中,我们评估了亚硒酸钠是否调节调节性 T 细胞分化。通过流式细胞术评估了在存在或不存在硒(以亚硒酸钠(2.0×10M)的形式)的情况下,CD4+T 细胞培养物中 IL-2 和 TGF-β刺激下 CD4+CD25+Foxp3+、CD4+CD25+和 CD4+CTLA-4+细胞在 CD4+T 细胞中的百分比。通过 RT-qPCR 分析 TET2/3 酶和 IL-10 的 mRNA 表达,并通过 ELISA 测量 IL-10 水平。我们观察到在存在硒的情况下 CD4+CD25+Foxp3+和 CD4+CTLA-4+细胞减少。然而,在去除硒后,正常百分比再次达到。在缺乏 IL-2 和 TGF-β的情况下,在硒预刺激的细胞培养物中检测到 CD4+CTL4-4+细胞增加。此外,我们观察到在存在硒的情况下 TET3 减少。最后,我们观察到在暴露于硒的培养物中转录和蛋白水平以及 TET2 的相对表达增加。我们认为硒可在体外可逆地影响调节性 T 细胞分化。同样,硒可能调节 Treg 百分比,促进最佳免疫反应,同时表达特异性抑制分子。

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本文引用的文献

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IL-4 enhances IL-10 production in Th1 cells: implications for Th1 and Th2 regulation.IL-4 增强 Th1 细胞中 IL-10 的产生:对 Th1 和 Th2 调节的影响。
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Vitamin C Facilitates Demethylation of the Foxp3 Enhancer in a Tet-Dependent Manner.维生素C以Tet依赖的方式促进Foxp3增强子的去甲基化。
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Down-regulation of Tet2 prevents TSDR demethylation in IL2 deficient regulatory T cells.
Tet2 的下调可防止 IL2 缺陷型调节性 T 细胞中 TSDR 的去甲基化。
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Active demethylation of the Foxp3 locus leads to the generation of stable regulatory T cells within the thymus.Foxp3 基因座的活性去甲基化导致胸腺内稳定的调节性 T 细胞的产生。
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IL-10+ CTLA-4+ Th2 inhibitory cells form in a Foxp3-independent, IL-2-dependent manner from Th2 effectors during chronic inflammation.IL-10+ CTLA-4+ Th2 抑制性细胞在慢性炎症过程中从 Th2 效应物中以 Foxp3 非依赖性、IL-2 依赖性方式形成。
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Two modes of immune suppression by Foxp3(+) regulatory T cells under inflammatory or non-inflammatory conditions.Foxp3(+) 调节性 T 细胞在炎症或非炎症条件下的两种免疫抑制模式。
Semin Immunol. 2011 Dec;23(6):424-30. doi: 10.1016/j.smim.2011.10.002. Epub 2011 Nov 3.
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Cutting edge: mechanisms of IL-2-dependent maintenance of functional regulatory T cells.前沿:IL-2 依赖性维持功能性调节性 T 细胞的机制。
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Dietary selenium modulates activation and differentiation of CD4+ T cells in mice through a mechanism involving cellular free thiols.膳食硒通过涉及细胞游离巯基的机制调节小鼠 CD4+T 细胞的激活和分化。
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