Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, State University of New York, Buffalo, New York, USA.
WIREs Mech Dis. 2023 Nov-Dec;15(6):e1627. doi: 10.1002/wsbm.1627. Epub 2023 Aug 10.
Transcription factors are crucial to regulate gene expression in immune cells and in other cell types. In lymphocytes, there are a large number of different transcription factors that are known to contribute to cell differentiation and the balance between quiescence and activation. One such transcription factor is E26 oncogene homolog 1 (Ets1). Ets1 expression is high in quiescent B and T lymphocytes and its levels are decreased upon activation. The human ETS1 gene has been identified as a susceptibility locus for many autoimmune and inflammatory diseases. In accord with this, gene knockout of Ets1 in mice leads to development of a lupus-like autoimmune disease, with enhanced activation and differentiation of both B cells and T cells. Prior reviews have summarized functional roles for Ets1 based on studies of Ets1 knockout mice. In recent years, numerous additional studies have been published that further validate ETS1 as a susceptibility locus for human diseases where immune dysregulation plays a causative role. In this update, new information that further links Ets1 to human autoimmune diseases is organized and collated to serve as a resource. This update also describes recent studies that seek to understand molecularly how Ets1 regulates immune cell activation, either using human cells and tissues or mouse models. This resource is expected to be useful to investigators seeking to understand how Ets1 may regulate the human immune response, particularly in terms of its roles in autoimmunity and inflammation. This article is categorized under: Immune System Diseases > Genetics/Genomics/Epigenetics Immune System Diseases > Molecular and Cellular Physiology.
转录因子对于调节免疫细胞和其他细胞类型中的基因表达至关重要。在淋巴细胞中,有大量已知的转录因子有助于细胞分化以及静止和激活之间的平衡。一种这样的转录因子是 E26 致癌基因同源物 1(Ets1)。Ets1 在静止的 B 和 T 淋巴细胞中表达水平较高,而在激活后其水平降低。人类 ETS1 基因已被确定为许多自身免疫和炎症性疾病的易感基因座。与此一致,在小鼠中敲除 Ets1 基因会导致狼疮样自身免疫性疾病的发展,B 细胞和 T 细胞的激活和分化增强。之前的综述根据 Ets1 敲除小鼠的研究总结了 Ets1 的功能作用。近年来,发表了许多其他研究进一步证实了 ETS1 是人类疾病的易感基因座,其中免疫失调起着因果作用。在本次更新中,将组织和整理与 Ets1 与人类自身免疫性疾病进一步相关的新信息,作为一种资源。本更新还描述了最近的研究,旨在使用人类细胞和组织或小鼠模型来了解 Ets1 如何调节免疫细胞激活的分子机制。预计这个资源对于寻求了解 Ets1 如何调节人类免疫反应的研究人员,特别是在其自身免疫和炎症中的作用,将是有用的。本文归入:免疫系统疾病>遗传学/基因组学/表观遗传学 免疫系统疾病>分子和细胞生理学。