The molecular basis of immune regulation in autoimmunity

Clin Sci (Lond). 2018 Jan 5;132(1):43-67. doi: 10.1042/CS20171154. Print 2018 Jan 16.

Abstract

Autoimmune diseases can be triggered and modulated by various molecular and cellular characteristics. The mechanisms of autoimmunity and the pathogenesis of autoimmune diseases have been investigated for several decades. It is well accepted that autoimmunity is caused by dysregulated/dysfunctional immune susceptible genes and environmental factors. There are multiple physiological mechanisms that regulate and control self-reactivity, but which can also lead to tolerance breakdown when in defect. The majority of autoreactive T or B cells are eliminated during the development of central tolerance by negative selection. Regulatory cells such as Tregs (regulatory T) and MSCs (mesenchymal stem cells), and molecules such as CTLA-4 (cytotoxic T-lymphocyte associated antigen 4) and IL (interleukin) 10 (IL-10), help to eliminate autoreactive cells that escaped to the periphery in order to prevent development of autoimmunity. Knowledge of the molecular basis of immune regulation is needed to further our understanding of the underlying mechanisms of loss of tolerance in autoimmune diseases and pave the way for the development of more effective, specific, and safer therapeutic interventions.

Keywords: Autoreactive lymphocytes; Immune tolerance; T regulatory cells; autoimmunity; immunomodulation; molecular basis of health and disease.

Publication types

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

MeSH terms

  • Autoimmunity / genetics*
  • Autoimmunity / immunology*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • CTLA-4 Antigen / immunology
  • CTLA-4 Antigen / metabolism
  • Gene Expression / immunology*
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Immune Tolerance / genetics
  • Immune Tolerance / immunology
  • Mesenchymal Stem Cells / immunology
  • Mesenchymal Stem Cells / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism

Substances

  • CTLA-4 Antigen
  • CTLA4 protein, human