PR002724 (Project)

Description:The polarization of macrophages into distinct functional phenotypes, namely the pro-inflammatory M1 and the pro-reparative M2 states, is a critical determinant in immune response and disease pathogenesis. This process is underpinned by profound metabolic reprogramming, with the lipidome being increasingly recognized as a key regulator and readout of macrophage function. Interferon regulatory factor 7 (IRF7), a transcription factor well-known for its master role in type I interferon signaling, has recently been implicated in immune cell differentiation and metabolic regulation. However, its specific function in governing the lipid metabolic landscape during human macrophage polarization remains largely unexplored. The primary goal of this project was to define the specific impact of IRF7 overexpression on the lipidome of human macrophages and to elucidate its role in polarization. We utilized a model of THP-1-derived macrophages to test the central hypothesis that enforced expression of IRF7 drives a distinct lipid remodeling program, which in turn contributes to a specific macrophage polarization phenotype. This study aimed to provide a comprehensive, untargeted lipidomic profile following IRF7 overexpression, thereby bridging the gap between IRF7 signaling and metabolic regulation in macrophages. Our lipidomic analysis successfully identified a unique and significant alteration in the lipid profile of IRF7-overexpressing macrophages. We observed specific shifts in key lipid classes, which are consistent with the M2-like macrophages lipidomic profile. These findings provide the first evidence, to our knowledge, that IRF7 is a potent regulator of lipid metabolism in human macrophages.