The critical role of epigenetics in systemic lupus erythematosus and autoimmunity

Hai Long, Heng Yin, Ling Wang, M. Eric Gershwin, Qianjin Lu

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

One of the major disappointments in human autoimmunity has been the relative failure on genome-wide association studies to provide "smoking genetic guns" that would explain the critical role of genetic susceptibility to loss of tolerance. It is well known that autoimmunity refers to the abnormal state that the dysregulated immune system attacks the healthy cells and tissues due to the loss of immunological tolerance to self-antigens. Its clinical outcomes are generally characterized by the presence of autoreactive immune cells and (or) the development of autoantibodies, leading to various types of autoimmune disorders. The etiology and pathogenesis of autoimmune diseases are highly complex. Both genetic predisposition and environmental factors such as nutrition, infection, and chemicals are implicated in the pathogenic process of autoimmunity, however, how much and by what mechanisms each of these factors contribute to the development of autoimmunity remain unclear. Epigenetics, which refers to potentially heritable changes in gene expression and function that do not involve alterations of the DNA sequence, has provided us with a brand new key to answer these questions. In the recent decades, increasing evidence have demonstrated the roles of epigenetic dysregulation, including DNA methylation, histone modification, and noncoding RNA, in the pathogenesis of autoimmune diseases, especially systemic lupus erythematosus (SLE), which have shed light on a new era for autoimmunity research. Notably, DNA hypomethylation and reactivation of the inactive X chromosome are two epigenetic hallmarks of SLE. We will herein discuss briefly how genetic studies fail to completely elucidate the pathogenesis of autoimmune diseases and present a comprehensive review on landmark epigenetic findings in autoimmune diseases, taking SLE as an extensively studied example. The epigenetics of other autoimmune diseases such as rheumatic arthritis, systemic sclerosis and primary biliary cirrhosis will also be summarized. Importantly we emphasize that the stochastic processes that lead to DNA modification may be the lynch pins that drive the initial break in tolerance.

Original languageEnglish (US)
JournalJournal of Autoimmunity
DOIs
StateAccepted/In press - Jun 24 2016

Fingerprint

Autoimmunity
Epigenomics
Systemic Lupus Erythematosus
Autoimmune Diseases
Genetic Predisposition to Disease
Histone Code
Stochastic Processes
Untranslated RNA
Rheumatic Fever
Biliary Liver Cirrhosis
Systemic Scleroderma
Genome-Wide Association Study
DNA
Autoantigens
Firearms
X Chromosome
DNA Methylation
Autoantibodies
Immune System
Smoking

Keywords

  • Autoimmune disease
  • DNA demethylation
  • DNA methylation
  • Epigenetics
  • Histone modification
  • MicroRNA
  • Systemic lupus erythematosus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

The critical role of epigenetics in systemic lupus erythematosus and autoimmunity. / Long, Hai; Yin, Heng; Wang, Ling; Gershwin, M. Eric; Lu, Qianjin.

In: Journal of Autoimmunity, 24.06.2016.

Research output: Contribution to journalArticle

@article{8f86215fea734382a32249e2c7d6f2d5,
title = "The critical role of epigenetics in systemic lupus erythematosus and autoimmunity",
abstract = "One of the major disappointments in human autoimmunity has been the relative failure on genome-wide association studies to provide {"}smoking genetic guns{"} that would explain the critical role of genetic susceptibility to loss of tolerance. It is well known that autoimmunity refers to the abnormal state that the dysregulated immune system attacks the healthy cells and tissues due to the loss of immunological tolerance to self-antigens. Its clinical outcomes are generally characterized by the presence of autoreactive immune cells and (or) the development of autoantibodies, leading to various types of autoimmune disorders. The etiology and pathogenesis of autoimmune diseases are highly complex. Both genetic predisposition and environmental factors such as nutrition, infection, and chemicals are implicated in the pathogenic process of autoimmunity, however, how much and by what mechanisms each of these factors contribute to the development of autoimmunity remain unclear. Epigenetics, which refers to potentially heritable changes in gene expression and function that do not involve alterations of the DNA sequence, has provided us with a brand new key to answer these questions. In the recent decades, increasing evidence have demonstrated the roles of epigenetic dysregulation, including DNA methylation, histone modification, and noncoding RNA, in the pathogenesis of autoimmune diseases, especially systemic lupus erythematosus (SLE), which have shed light on a new era for autoimmunity research. Notably, DNA hypomethylation and reactivation of the inactive X chromosome are two epigenetic hallmarks of SLE. We will herein discuss briefly how genetic studies fail to completely elucidate the pathogenesis of autoimmune diseases and present a comprehensive review on landmark epigenetic findings in autoimmune diseases, taking SLE as an extensively studied example. The epigenetics of other autoimmune diseases such as rheumatic arthritis, systemic sclerosis and primary biliary cirrhosis will also be summarized. Importantly we emphasize that the stochastic processes that lead to DNA modification may be the lynch pins that drive the initial break in tolerance.",
keywords = "Autoimmune disease, DNA demethylation, DNA methylation, Epigenetics, Histone modification, MicroRNA, Systemic lupus erythematosus",
author = "Hai Long and Heng Yin and Ling Wang and Gershwin, {M. Eric} and Qianjin Lu",
year = "2016",
month = "6",
day = "24",
doi = "10.1016/j.jaut.2016.06.020",
language = "English (US)",
journal = "Journal of Autoimmunity",
issn = "0896-8411",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - The critical role of epigenetics in systemic lupus erythematosus and autoimmunity

AU - Long, Hai

AU - Yin, Heng

AU - Wang, Ling

AU - Gershwin, M. Eric

AU - Lu, Qianjin

PY - 2016/6/24

Y1 - 2016/6/24

N2 - One of the major disappointments in human autoimmunity has been the relative failure on genome-wide association studies to provide "smoking genetic guns" that would explain the critical role of genetic susceptibility to loss of tolerance. It is well known that autoimmunity refers to the abnormal state that the dysregulated immune system attacks the healthy cells and tissues due to the loss of immunological tolerance to self-antigens. Its clinical outcomes are generally characterized by the presence of autoreactive immune cells and (or) the development of autoantibodies, leading to various types of autoimmune disorders. The etiology and pathogenesis of autoimmune diseases are highly complex. Both genetic predisposition and environmental factors such as nutrition, infection, and chemicals are implicated in the pathogenic process of autoimmunity, however, how much and by what mechanisms each of these factors contribute to the development of autoimmunity remain unclear. Epigenetics, which refers to potentially heritable changes in gene expression and function that do not involve alterations of the DNA sequence, has provided us with a brand new key to answer these questions. In the recent decades, increasing evidence have demonstrated the roles of epigenetic dysregulation, including DNA methylation, histone modification, and noncoding RNA, in the pathogenesis of autoimmune diseases, especially systemic lupus erythematosus (SLE), which have shed light on a new era for autoimmunity research. Notably, DNA hypomethylation and reactivation of the inactive X chromosome are two epigenetic hallmarks of SLE. We will herein discuss briefly how genetic studies fail to completely elucidate the pathogenesis of autoimmune diseases and present a comprehensive review on landmark epigenetic findings in autoimmune diseases, taking SLE as an extensively studied example. The epigenetics of other autoimmune diseases such as rheumatic arthritis, systemic sclerosis and primary biliary cirrhosis will also be summarized. Importantly we emphasize that the stochastic processes that lead to DNA modification may be the lynch pins that drive the initial break in tolerance.

AB - One of the major disappointments in human autoimmunity has been the relative failure on genome-wide association studies to provide "smoking genetic guns" that would explain the critical role of genetic susceptibility to loss of tolerance. It is well known that autoimmunity refers to the abnormal state that the dysregulated immune system attacks the healthy cells and tissues due to the loss of immunological tolerance to self-antigens. Its clinical outcomes are generally characterized by the presence of autoreactive immune cells and (or) the development of autoantibodies, leading to various types of autoimmune disorders. The etiology and pathogenesis of autoimmune diseases are highly complex. Both genetic predisposition and environmental factors such as nutrition, infection, and chemicals are implicated in the pathogenic process of autoimmunity, however, how much and by what mechanisms each of these factors contribute to the development of autoimmunity remain unclear. Epigenetics, which refers to potentially heritable changes in gene expression and function that do not involve alterations of the DNA sequence, has provided us with a brand new key to answer these questions. In the recent decades, increasing evidence have demonstrated the roles of epigenetic dysregulation, including DNA methylation, histone modification, and noncoding RNA, in the pathogenesis of autoimmune diseases, especially systemic lupus erythematosus (SLE), which have shed light on a new era for autoimmunity research. Notably, DNA hypomethylation and reactivation of the inactive X chromosome are two epigenetic hallmarks of SLE. We will herein discuss briefly how genetic studies fail to completely elucidate the pathogenesis of autoimmune diseases and present a comprehensive review on landmark epigenetic findings in autoimmune diseases, taking SLE as an extensively studied example. The epigenetics of other autoimmune diseases such as rheumatic arthritis, systemic sclerosis and primary biliary cirrhosis will also be summarized. Importantly we emphasize that the stochastic processes that lead to DNA modification may be the lynch pins that drive the initial break in tolerance.

KW - Autoimmune disease

KW - DNA demethylation

KW - DNA methylation

KW - Epigenetics

KW - Histone modification

KW - MicroRNA

KW - Systemic lupus erythematosus

UR - http://www.scopus.com/inward/record.url?scp=84979656440&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84979656440&partnerID=8YFLogxK

U2 - 10.1016/j.jaut.2016.06.020

DO - 10.1016/j.jaut.2016.06.020

M3 - Article

JO - Journal of Autoimmunity

JF - Journal of Autoimmunity

SN - 0896-8411

ER -