Year: 2025
Type: article
Abstract: The cytochrome-b5 reductases (CYB5Rs) regulate cellular redox balance and contribute to the pathogenesis of inflammatory diseases. However, the roles of CYB5R5 in macrophages remain poorly understood and require further elucidation. In this study, we revealed that CYB5R5 orchestrates macrophage inflammation by inhibiting interleukin (IL)-1β production from M1 macrophages. Mechanistically, CYB5R5 enhances flavin adenine dinucleotide (FAD)-lysine demethylase1 (LSD1) signaling to regulate the histone demethylation of complement component 1, q subcomponent (C1q)-coding genes, thereby lowering NLRP3 inflammasome assembly. We also found that myeloid depletion of Cyb5r5 in mice exacerbates inflammatory responses in LPS-induced sepsis. This study reveals that CYB5R5 attenuates M1 macrophage polarization via metabolic and epigenetic reprogramming mechanism, thus providing potential therapeutic targets for macrophage-mediated inflammatory disorders.
Source: Cell Death and Disease
Authors: Jian Fu, Zhihua Liu, Hangchao Zhang, Xinmei Zhang, Shijie Liu, Xuehua Mei, Xiu Zeng, Wenkai Ren
Institution: South China Agricultural University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,990
Award: G8780081657
OpenAlex ID: W4415404379