Rédiger un PREreview

During the innate immune response at epithelial wound sites, oxidative stress acts microbicidal and—mechanistically less well understood—as an immune and resilience signal. The reversible sulfhydryl (SH) oxidation of kinases, phosphatases, and transcription factors constitute the perhaps best-known redox signalling paradigm, whereas mechanisms that transduce metabolic redox cues, such as redox cofactor balance, remain little explored.

Here, using mammalian cells, microsomes, and live zebrafish, we identify DHRS7, a short-chain fatty acid dehydrogenase/reductase (SDR), as conserved, 5-hydroxyeicosanoid dehydrogenase (5-HEDH). Under oxidative stress, DHRS7 consumes NADP ⁺ to convert arachidonic acid (AA)-derived 5(S)-HETE into the inflammatory lipid 5-KETE, which activates leukocyte chemotaxis via the OXER1 receptor. While Dhrs7 acts as a NADPH-dependent 5-KETE sink in unstressed, healthy tissue, it promotes rapid, 5-KETE dependent leukocytic inflammation in wounded zebrafish skin.

Thus, DHRS7 epitomizes an underappreciated mode of redox signalling—beyond classic SH oxidation—that leverages NADPH metabolism to generate or quench a paracrine lipid signal. Metabolic redox sensors like DHRS7 might be promising therapeutic targets in diseases characterized by disturbed redox balance.