An update on the roles of transcription factor Ets1 in autoimmune diseases

Author:

Garrett‐Sinha Lee Ann1ORCID

Affiliation:

1. Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences State University of New York Buffalo New York USA

Abstract

AbstractTranscription 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

Funder

National Institutes of Health

Publisher

Wiley

Subject

Cell Biology,Medicine (miscellaneous)

Reference118 articles.

1. For further details the reader is directed to the references herein which describe each of the studies in more detail. The role of Ets1 in autoimmune diseases has also been previously reviewed: (Gallant & Gilkeson 2006; Garrett‐Sinha  2013; Garrett‐Sinha et al.  2016; Leng et al.  2011). For further information on GWAS and autoimmune diseases the reader is referred to these references: (Fike et al.  2019; Suzuki et al.  2021). For further information on miRNA roles in autoimmunity the reader is referred to these references: (Xiao et al.  2020; Zhang et al.  2020).

2. Characterization of Rheumatoid Arthritis Risk-Associated SNPs and Identification of Novel Therapeutic Sites Using an In-Silico Approach

3. The Ets-1 Transcription Factor Is Required for the Development of Natural Killer Cells in Mice

4. Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus

5. Increased T-cell apoptosis and terminal B-cell differentiation induced by inactivation of the Ets-1 proto-oncogene

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