Immune enzyme shields healthy cells from inflammation in zebrafish

Scientists at Memorial Sloan Kettering Cancer Center identified the gene responsible for a long-sought enzyme involved in regulating 5-oxoETE, a signalling molecule that attracts white blood cells to sites of infection. The study was published in Nature.

Why mice weren’t enough

The gene, called DHRS7, was identified as responsible for making the enzyme after researchers systematically switched off candidate genes in human cells. Mice and rats lack a known receptor for 5-oxoETE, meaning this signalling system does not fully function in those animals. Zebrafish do have the receptor, making them the right model to study the system in a living organism.

The discovery brought together two separate research lines in the same laboratory. While one researcher tracked down the mysterious enzyme, another was using zebrafish to study colitis, disabling selected genes to understand how they influenced intestinal inflammation. Removing the receptor was expected to reduce inflammation. Instead, the fish developed spontaneous gut inflammation with no infection present. The same happened when DHRS7 was disabled: inflammation increased rather than decreased.

A protective function, not just activation

That unexpected result led to a new interpretation. The 5-oxoETE signal does not only recruit immune cells, it also helps prevent those same cells from damaging surrounding healthy tissue. When the signal is disrupted, the body loses a brake on its own immune response. The researchers suggest this insight may be relevant for conditions involving runaway inflammation, such as inflammatory bowel disease and asthma. What this means for treatment development requires further investigation.

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