The role of AhR in autoimmune regulation and its potential as a therapeutic target against CD4 T cell mediated inflammatory disorder

Int J Mol Sci. 2014 Jun 5;15(6):10116-35. doi: 10.3390/ijms150610116.

Abstract

AhR has recently emerged as a critical physiological regulator of immune responses affecting both innate and adaptive systems. Since the AhR signaling pathway represents an important link between environmental stimulators and immune-mediated inflammatory disorder, it has become the object of great interest among researchers recently. The current review discusses new insights into the mechanisms of action of a select group of inflammatory autoimmune diseases and the ligand-activated AhR signaling pathway. Representative ligands of AhR, both exogenous and endogenous, are also reviewed relative to their potential use as tools for understanding the role of AhR and as potential therapeutics for the treatment of various inflammatory autoimmune diseases, with a focus on CD4 helper T cells, which play important roles both in self-immune tolerance and in inflammatory autoimmune diseases. Evidence indicating the potential use of these ligands in regulating inflammation in various diseases is highlighted, and potential mechanisms of action causing immune system effects mediated by AhR signaling are also discussed. The current review will contribute to a better understanding of the role of AhR and its signaling pathway in CD4 helper T cell mediated inflammatory disorder. Considering the established importance of AhR in immune regulation and its potential as a therapeutic target, we also think that both further investigation into the molecular mechanisms of immune regulation that are mediated by the ligand-specific AhR signaling pathway, and integrated research and development of new therapeutic drug candidates targeting the AhR signaling pathway should be pursued urgently.

Publication types

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

MeSH terms

  • Animals
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / immunology*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • Drug Discovery / methods
  • Humans
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Ligands
  • Molecular Targeted Therapy / methods
  • Receptors, Aryl Hydrocarbon / immunology*
  • Signal Transduction / drug effects

Substances

  • Ligands
  • Receptors, Aryl Hydrocarbon