A Review of the Role of Activated Peroxisome Proliferator-Activated Receptors (PPARs) in Regulating Immune Responses and Their Targeting for the Treatment of Immune-Related Disease

Peroxisome proliferator-activated receptors (PPARs), belonging to the superfamily of nuclear receptors, serve as transcription factors upon ligand binding, either with endogenous or synthetic ligands, forming heterodimers with Retinoid X Receptors (RXRs). They initiate gene transcription to harmonize lipid and carbohydrate metabolism with cell proliferation and differentiation. Fatty acids and their derivatives are natural ligands. To date, three subtypes of PPARs have been identified: PPARα, PPARγ, and PPARβ/δ, each having drug agonists and antagonists developed. Furthermore, universal agonists have been designed to target combinations of these subgroups to mitigate drug side effects. PPARs control cellular energy homeostasis and are also expressed in immune cells, where they play a vital role in their differentiation and fate. Given the significant impact of PPAR activity on both innate and adaptive immune cell function and their involvement in immune-related diseases, e.g. antiphospholipid syndrome, hepatitis, myocarditis, neurodegenerative diseases, psoriasis, asthma, inflammatory bowel disease, renal inflammation and atherosclerosis, it is conceivable to treat some of these diseases by modulating these transcription factors. Furthermore, due to the significance role of PPARs in regulating tissue metabolism, several instances of them have been investigated.