Emerging roles of PPARS in inflammation and immunity

Key Points Peroxisome proliferator-activated receptors (PPARs) are ligand-inducible transcription factors that belong to the nuclear-hormone-receptor superfamily. The PPARs can positively regulate gene transcription through their ability to heterodimerize with 9- cis -retinoic acid receptor (RXR) and bind to specific DNA sequences in the promoter regions of selective genes, known as peroxisome proliferator response elements (PPREs). PPARs can negatively regulate gene transcription through their ability to antagonize several important signalling pathways using various transrepression mechanisms. Activated PPARs regulate the inflammatory response through their ability to regulate the expression of several genes that are involved in inflammation. The PPARs are expressed in a wide variety of tissues and cells of the immune system, including macrophages, dendritic cells (DCs), T cells and B cells. The PPARs are important for the regulation of the immune response. This arises through the ability of these receptors to regulate DC and T-cell cytokine production, as well as lymphocyte proliferation. Lipids and lipid metabolism have well-documented regulatory effects on inflammatory processes. Recent work has highlighted the role of the peroxisome proliferator-activated receptors (PPARs) — a subset of the nuclear-hormone-receptor superfamily that are activated by various lipid species — in regulating inflammatory responses. Here, we describe how the PPARs, through their interactions with transcription factors and other cell-signalling systems, have important regulatory roles in innate and adaptive immunity.