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溃疡性结肠炎患者调节性T细胞中微小RNA表达改变及免疫抑制细胞因子产生

Altered microRNA Expression and Immunosuppressive Cytokine Production by Regulatory T Cells of Ulcerative Colitis Patients.

作者信息

Mohammadnia-Afrouzi Mousa, Hosseini Ahmad Zavaran, Khalili Ali, Abediankenari Saeid, Amari Afshin, Aghili Babak, Nataj Hadi Hossein

机构信息

a Department of Immunology, Faculty of Medical Sciences , Tarbiat Modares University , Tehran , Iran.

b Department of Immunology , Mazandaran University of Medical Sciences , Sari , Iran.

出版信息

Immunol Invest. 2016;45(1):63-74. doi: 10.3109/08820139.2015.1103749.

Abstract

Regulatory T (Treg) cells are essential for maintenance of peripheral tolerance and prevention of autoimmune diseases in part by producing immunosuppressive cytokines. Recently, microRNAs (miRNAs) have also been involved in autoimmune disorders, not least for their crucial role in the regulation of Treg biology and function. We simultaneously investigated the concentration of IL-35, IL-10, TGF-β, and sCD25 in supernatant of cell culture and the expression patterns of several miRNAs in CD4(+)CD25(+) CD127(-/low) FoxP3(+) Tregs of ulcerative colitis (UC) patients. Significantly lower levels of IL-10 and IL-35 were observed in Treg cultures of UC patients. miR-21, miR-146a, and miR-155 levels were downregulated and miR-31 level was upregulated in Tregs of patients. Our results suggest that microRNAs may serve as a novel regulator in function and homoeostasis of UC Treg cells, providing a key role for them in pathophysiology of UC.

摘要

调节性T(Treg)细胞对于维持外周免疫耐受和预防自身免疫性疾病至关重要,部分原因是其能产生免疫抑制性细胞因子。近来,微小RNA(miRNA)也参与了自身免疫性疾病,尤其是因其在Treg生物学和功能调节中发挥的关键作用。我们同时研究了细胞培养上清液中白细胞介素-35(IL-35)、白细胞介素-10(IL-10)、转化生长因子-β(TGF-β)和可溶性白细胞介素-2受体α链(sCD25)的浓度,以及溃疡性结肠炎(UC)患者CD4(+)CD25(+)CD127(-/low)FoxP3(+)调节性T细胞中几种miRNA的表达模式。在UC患者的调节性T细胞培养物中观察到IL-10和IL-35水平显著降低。患者调节性T细胞中miR-21、miR-146a和miR-155水平下调,而miR-31水平上调。我们的结果表明,微小RNA可能作为UC调节性T细胞功能和体内平衡的新型调节因子,在UC的病理生理学中发挥关键作用。

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