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人类 B 淋巴细胞中自身免疫性疾病的 DNA 甲基化特征。

DNA methylation signatures of autoimmune diseases in human B lymphocytes.

机构信息

Graduate Institute of Biomedical Sciences, China Medical University, No. 91, Xueshi Road, North District, Taichung City, Taïwan 404, Taichung, Taiwan.

出版信息

Clin Immunol. 2021 Jan;222:108622. doi: 10.1016/j.clim.2020.108622. Epub 2020 Nov 12.

Abstract

B lymphocytes play key roles in adaptive and innate immunity. In autoimmune diseases, their participation in disease instigation and/or progression has been demonstrated in both experimental models and clinical trials. Recent epigenetic investigations of human B lymphocyte subsets revealed the importance of DNA methylation in exquisitely regulating the cellular activation and differentiation programs. This review discusses recent advances on the potential of DNA methylation to shape events that impart generation of plasma cells and memory B cells, providing novel insight into homeostatic regulation of the immune system. In parallel, epigenetic profiling of B cells from patients with systemic or organo-specific autoimmune diseases disclosed distinctive differential methylation regions that, in some cases, could stratify patients from controls. Development of tools for editing DNA methylation in the mammalian genome could be useful for future functional studies of epigenetic regulation by offering the possibility to edit locus-specific methylation, with potential translational applications.

摘要

B 淋巴细胞在适应性和先天性免疫中发挥关键作用。在自身免疫性疾病中,它们在实验模型和临床试验中的疾病引发和/或进展中的参与已得到证实。最近对人类 B 淋巴细胞亚群的表观遗传研究揭示了 DNA 甲基化在精细调控细胞激活和分化程序中的重要性。这篇综述讨论了 DNA 甲基化在塑造浆细胞和记忆 B 细胞生成方面的潜力的最新进展,为免疫系统的动态平衡调控提供了新的见解。同时,对系统性或器官特异性自身免疫性疾病患者的 B 细胞进行的表观遗传分析揭示了独特的差异甲基化区域,在某些情况下,这些区域可以将患者与对照组区分开来。开发用于编辑哺乳动物基因组中 DNA 甲基化的工具可能对通过提供编辑特定基因座甲基化的可能性来研究表观遗传调控的功能具有重要意义,具有潜在的转化应用。

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