Regulation of T-Cell Signaling by Post-Translational Modifications in Autoimmune Disease

Int J Mol Sci. 2018 Mar 12;19(3):819. doi: 10.3390/ijms19030819.

Abstract

The adaptive immune system involves antigen-specific host defense mechanisms mediated by T and B cells. In particular, CD4⁺ T cells play a central role in the elimination of pathogens. Immunological tolerance in the thymus regulates T lymphocytes to avoid self-components, including induction of cell death in immature T cells expressing the self-reactive T-cell receptor repertoire. In the periphery, mature T cells are also regulated by tolerance, e.g., via induction of anergy or regulatory T cells. Thus, T cells strictly control intrinsic signal transduction to prevent excessive responses or self-reactions. If the inhibitory effects of T cells on these mechanisms are disrupted, T cells may incorrectly attack self-components, which can lead to autoimmune disease. The functions of T cells are supported by post-translational modifications, particularly phosphorylation, of signaling molecules, the proper regulation of which is controlled by endogenous mechanisms within the T cells themselves. In recent years, molecular targeted agents against kinases have been developed for treatment of autoimmune diseases. In this review, we discuss T-cell signal transduction in autoimmune disease and provide an overview of acetylation-mediated regulation of T-cell signaling pathways.

Keywords: T cell; autoimmune disease; post-translational modification.

Publication types

  • Review

MeSH terms

  • Acetylation
  • Animals
  • Autoimmune Diseases / metabolism*
  • Humans
  • Phosphorylation
  • Protein Processing, Post-Translational*
  • Signal Transduction*
  • T-Lymphocytes / metabolism*