The roles of PPARγ and its agonists in autoimmune diseases: A comprehensive review

J Autoimmun. 2020 Sep:113:102510. doi: 10.1016/j.jaut.2020.102510. Epub 2020 Jul 1.

Abstract

Autoimmune diseases are common diseases of the immune system that are characterized by the loss of self-tolerance and the production of autoantibodies; the breakdown of immune tolerance and the prolonged inflammatory reaction are undisputedly core steps in the initiation and maintenance of autoimmunity. Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors that belong to the nuclear hormone receptor family and act as ligand-activated transcription factors. There are three different isotypes of PPARs: PPARα, PPARγ, and PPARβ/δ. PPARγ is an established regulator of glucose homeostasis and lipid metabolism. Recent studies have demonstrated that PPARγ exhibits anti-inflammatory and anti-fibrotic effects in multiple disease models. PPARγ can also modulate the activation and polarization of macrophages, regulate the function of dendritic cells and mediate T cell survival, activation, and differentiation. In this review, we summarize the signaling pathways and biological functions of PPARγ and focus on how PPARγ and its agonists play protective roles in autoimmune diseases, including autoimmune thyroid diseases, multiple sclerosis, rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus, primary Sjogren syndrome and primary biliary cirrhosis.

Keywords: Autoimmune diseases; Nuclear hormone receptors; PPARγ.

Publication types

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

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / immunology*
  • Disease Models, Animal
  • Glucose / metabolism
  • Humans
  • Lipid Metabolism / drug effects
  • Lipid Metabolism / immunology
  • PPAR gamma / agonists
  • PPAR gamma / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / immunology

Substances

  • Anti-Inflammatory Agents
  • PPAR gamma
  • Glucose