CYB5R5 Regulates IL-1beta Production in Macrophages (PRJCA034457)
The cytochrome-b5 reductases (CYB5Rs) regulate redox balance in cells and have been implicated in the pathogenesis of inflammatory diseases affecting both the central nervous system and peripheral tissues. However, the subcellular localization and functional role of CYB5R5 in macrophages remain poorly understood and require further elucidation. In this study, we demonstrated that CYB5R5 orchestrates macrophage inflammation. CYB5R5 inhibits interleukin (IL)-1ß production from inflammatory macrophages. Mechanistically, CYB5R5 enhances FAD-lysine demethylase1 (LSD1) signaling to regulate the histone demethylation of C1q-coding genes, lowering the formation of NLRP3-ASC-Caspase-1 complex. We also found that mice with myeloid depletion of Cyb5r5 exacerbates inflammatory responses in LPS-induced sepsis. Our study proves that CYB5R5 is potential in lessening the pro-inflammatory macrophage responses associating with metabolic and epigenetic reprogramming, thus providing potential therapeutic targets for treating macrophage-related inflammatory diseases.