Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor family. After activation by specific ligands, they regulate the transcription of genes involved in lipid and lipoprotein metabolism, glucose and energy homeostasis,as well as cellular differentiation. Most studies have identified expression of the three PPARs in all cells of the arterial wall, where they control cholesterol homeostasis as well as the inflammatory response and, as a consequence, modulate atherogenesis. More generally, PPARs influence cell proliferation as well as the immune and inflammatory response in different tissues and cells.

PPARs regulate transcription of target genes involved in lipid and lipoprotein metabolism, glucose homeostasis and cell differentiation (particularly adipogenesis). Moreover, PPARs inhibit the activation of certain inflammatory response genes acting as transrepressors.The central role of PPARs as transcriptional mediators in the regulation of important metabolic process that influence 

cardiovascular risk, namely obesity and lipid metabolism, has been recently reviewed.2 In this article we will focus on the functions of PPARs in inflammation and associated disorders.

Control of inflammation by PPARs. PPARs are modulators of the inflammatory response in different cell types and tissues with potential therapeutic applications not only in atherosclerosis, but potentially also in other inflammation-related diseases, such as hepatic inflammation and inflammatory bowel disease.

The review of studies, published in Trends in Immunotherapy, focused on peroxisome proliferator-activated receptors (PPARs) activation as therapeutic targets in skin inflammation.Atopic dermatitis (AD) is a chronic and relapsing disease characterized by skin barrier dysfunction and immune dysregulation. Skin barrier disturbance is one of the exacerbation factors of AD, due to facile penetration of molecules such as antigens. From the aspect of immune dysregulation, innate and acquired immunity including cell proliferation, cell differentiation, and cytokine network are involved in the pathogenesis. In this review, the role of PPAR in AD and the possibility of its agonist for the treatment of AD are discussed.

References:

[1] https://www.nature.com/articles/0802499

[2] https://systems.enpress-publisher.com/index.php/ti/article/view/1063

[3] https://www.nature.com/articles/ncpendmet0397

[4] Chinetti G, Fruchart JC, Staels B. Peroxisome proliferatoractivated receptors (PPARs): nuclear receptors at the crossroads between lipid metabolism and inflammation. Inflamm Res 2000; 49: 497–505.

[5] Daynes, R., Jones, D. Emerging roles of PPARS in inflammation and immunity. Nat Rev Immunol 2, 748–759 (2002). https://doi.org/10.1038/nri912

[6] Francque, S., Szabo, G., Abdelmalek, M.F. et al. Nonalcoholic steatohepatitis: the role of peroxisome proliferator-activated receptors. Nat Rev Gastroenterol Hepatol 18, 24–39 (2021). https://doi.org/10.1038/s41575-020-00366-5.