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

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: PPAR alpha, PPAR gamma, and PPARf3/8. PPAR gamma is an established regulator of glucose homeostasis and lipid metabolism. Recent studies have demonstrated that PPAR gamma exhibits anti-inflammatory and anti-fibrotic effects in multiple disease models. PPAR gamma 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 PPAR gamma and focus on how PPAR gamma 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.