The first author of the study, published on October 7, 2026, in Nature, is Yanan Ma. The ScienceDaily report on the study is based on material from Memorial Sloan Kettering Cancer Center, the research institution involved.
For the study, the researchers examined live zebrafish and human cells and showed that DHRS7 either produces or breaks down the pro-inflammatory lipid 5-oxoETE, depending on the ratio of NADP+ to NADPH inside the cell. At wounds, where oxidative stress is high, the 5-oxoETE produced by DHRS7 rapidly alerts white blood cells with antimicrobial activity through the OXER1 receptor, while DHRS7 suppresses unnecessary inflammation in undamaged tissue with low NADP+ levels. According to the study authors, the entire chain begins with mechanical stress that releases the fatty acid arachidonic acid from cell membranes, from which 5-oxoETE is ultimately formed. Doctoral student Zaza Gelashvili describes the interplay as follows: physical stress releases the starting material, oxidative stress drives the conversion, and DHRS7 amplifies the signal.
A trail back to 1992
As the specialist news service Bioengineer.org reports, scientists at McGill University observed an enzyme that both produced and broke down 5-oxoETE as early as 1992, without being able to identify the corresponding human gene. A study from the same year showed that this enzyme converts 5(S)-HETE into 5-oxoETE using NADP+ and that the reaction is reversible because microsomes from human leukocytes reduce 5-oxoETE back to the starting substance using NADPH. Because mice still lack a known receptor for 5-oxoETE, the signaling pathway could not be studied in the standard model of biomedical research, whereas it is fully preserved in zebrafish.
The rodent version of DHRS7 showed almost no activity in experiments, which the researchers attribute to the absence of the receptor for 5-oxoETE in mice. The team switched to zebrafish.
Postdoctoral researcher Miklos Lengyel worked with a zebrafish model of colitis and switched off various genes to test their effects on intestinal inflammation. When he removed hcar1-4, the zebrafish version of the human receptor gene OXER1, inflammation unexpectedly occurred, even though the receptor for the alarm signal 5-oxoETE was absent and less, rather than more, inflammation would therefore have been expected. Removing the neutrophils that the signal normally attracts did not eliminate the inflammation either. When Lengyel instead silenced DHRS7 itself, inflammation increased again instead of subsiding as expected.
Protection through NUDIX hydrolases
The cause was a loss of cellular protection: without the 5-oxoETE signal or its receptor, the intestinal cells of the zebrafish became susceptible to the low level of chemical stress caused even by ordinary gut bacteria. According to the published study, 5-oxoETE induces the expression of NUDIX hydrolases, thereby preventing programmed cell death in both zebrafish and human intestinal cells.
According to a study abstract on bioRxiv dated February 8, 2025, DHRS7 promoted rapid, 5-KETE-dependent inflammation in wounded zebrafish skin. Even then, the authors described such metabolic redox sensors as potential therapeutic targets for diseases involving a disrupted redox balance. That study had thus already identified DHRS7 as the enzyme being sought around a year and a half before the Nature study; the new study now adds the protective mechanism in the intestine.
A commentary in the journal Free Radical Biology and Medicine proposes an approach to precision redox medicine that combines mechanistic specificity, biomarker-based patient stratification and targeted catalytic antioxidants. According to the Nature study's Reporting Summary, sample sizes were not determined in advance through power calculations, data collection and analysis were conducted without blinding the experimenters, and the human cell lines used were neither authenticated nor tested for possible mycoplasma contamination.
From an unknown enzyme in 1992 to an explained signaling pathway in 2026
Decades separate the first observation of the enzyme in human white blood cells in 1992 from the detailed description of its function in the current study. With DHRS7 now identified as the gene, it has been established that the signaling pathway both serves as an alarm signal and protects cells. Study co-author Miklos Lengyel considers it possible that targeted activation of this signaling pathway could increase the intestine's resilience to oxidative stress and thus mitigate damage caused by radiation therapy or chemotherapy, but stresses that further research is needed.