Scientists solve 30-year-old mystery and discover a hidden defense against inflammation — SkimNews
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- DHRS7 — Yanan Ma identified the human gene producing the enzyme behind 5-oxoETE signaling; disabling it in cultured human cells stopped the enzyme functioning, resolving a mystery that began at McGill University in 1992.
- Zebrafish — MSK researchers chose the fish over mice and rats because rodents lack a known receptor for 5-oxoETE; the rodent version of DHRS7 showed almost no enzyme activity, consistent with rodents having lost key functions in this pathway.
- hcar1-4 — Miklos Lengyel's knockout of the zebrafish version of human OXER1 caused intestinal inflammation with no infection present, the opposite of the expected reduction; removing neutrophils did not eliminate it.
- 5-oxoETE — blocking its production by disabling DHRS7 also increased inflammation, exposing a second role: helping tissues withstand the reactive substances immune cells release to kill pathogens, with zebrafish intestinal cells left vulnerable to stress from normal gut bacteria.
- Nature — the findings were published October 7, joining Ma's gene hunt with Lengyel's colitis experiments; lab head Philipp Niethammer said the paper brought together two separately led projects rather than one shared story.
- Memorial Sloan Kettering Cancer Center — the findings could advance research into cancer, inflammatory bowel disease and asthma, and raise the possibility of treatments that strengthen the body's natural defenses against inflammatory damage.
Why it matters: After more than 30 years without the gene, researchers on cancer, inflammatory bowel disease and asthma now have DHRS7 as a defined target and a counterintuitive principle: removing a molecule that starts inflammation can worsen tissue injury. The therapeutic direction shifts from blocking inflammation to reinforcing the body's own protective pathway.
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