The Emerging Epigenetic Role of CD8+T Cells in Autoimmune Diseases: A Systematic Review

Front Immunol. 2019 Apr 18:10:856. doi: 10.3389/fimmu.2019.00856. eCollection 2019.

Abstract

Autoimmune diseases are usually complex and multifactorial, characterized by aberrant production of autoreactive immune cells and/or autoantibodies against healthy cells and tissues. However, the pathogenesis of autoimmune diseases has not been clearly elucidated. The activation, differentiation, and development of CD8+ T cells can be affected by numerous inflammatory cytokines, transcription factors, and chemokines. In recent years, epigenetic modifications have been shown to play an important role in the fate of CD8+ T cells. The discovery of these modifications that contribute to the activation or suppression of CD8+ cells has been concurrent with the increasing evidence that CD8+ T cells play a role in autoimmunity. These relationships have been studied in various autoimmune diseases, including multiple sclerosis (MS), systemic sclerosis (SSc), type 1 diabetes (T1D), Grave's disease (GD), systemic lupus erythematosus (SLE), aplastic anemia (AA), and vitiligo. In each of these diseases, genes that play a role in the proliferation or activation of CD8+ T cells have been found to be affected by epigenetic modifications. Various cytokines, transcription factors, and other regulatory molecules have been found to be differentially methylated in CD8+ T cells in autoimmune diseases. These genes are involved in T cell regulation, including interferons, interleukin (IL),tumor necrosis factor (TNF), as well as linker for activation of T cells (LAT), cytotoxic T-lymphocyte-associated antigen 4 (CTLA4), and adapter proteins. MiRNAs also play a role in the pathogenesis of these diseases and several known miRNAs that are involved in these diseases have also been shown to play a role in CD8+ regulation.

Keywords: CD8+T cells; DNA methylation; MiRNAs; autoimmune diseases; epigenetics; histone modification.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology*
  • Autoimmunity / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / immunology
  • Epigenesis, Genetic / immunology*
  • Epigenomics / methods
  • Humans
  • T-Lymphocytes, Regulatory / immunology