Scientists have identified a receptor on sensory nerves that appears to detect a fatty-acid byproduct found at elevated levels in psoriatic skin. Blocking the receptor reduced itching and skin thickening in mice, suggesting that it could be a target for treatments for psoriasis and eczema, although further research is needed.
“Linoleic acid is a naturally occurring fatty acid found in foods ranging from nuts and seeds to vegetable oils,” said lead author Professor Santosh Mishra, a researcher at North Carolina State University’s College of Veterinary Medicine.
“Humans need to consume small amounts of linoleic acid, but excessive intake is associated with chronic heart disease and diabetes, among others.”
“We also know that certain polyunsaturated fat-derived molecules are associated with itch, and that linoleic acid is the most abundant polyunsaturated fat in both the skin and the Western diet.”
“We wanted to investigate the relationship between linoleic acid and itch.”
Tracing the itch pathway
Mishra and his colleagues had previously found that a linoleic acid derivative called EKODE, or 9-keto-12,13-epoxyoctadecenoic acid, was present at higher concentrations in psoriasis lesions than in unaffected skin. Injecting EKODE into mice caused them to scratch, but the mechanism by which the body detected the molecule was unclear.
The new study identifies Gpr35 as a possible detector. The receptor is found on a subset of sensory neurons involved in transmitting itch signals.
In cultured mouse neurons, EKODE triggered calcium signals—a marker of neuronal activation—in about 9% of cells. Chemically blocking Gpr35 or deleting the gene reduced these responses.
Mice genetically engineered to lack Gpr35 scratched much less after EKODE injections, while still responding normally to histamine, a classic itch trigger.
Effects in a psoriasis model
The researchers next used a standard mouse model of psoriasis, in which the drug imiquimod is applied to the skin. Mice lacking the receptor developed less skin thickening and scratched less than normal mice.
A single injection of a compound that inhibits Gpr35 also reduced scratching in normal mice with psoriasis-like or eczema-like skin.
The scientists further found that the neuropeptide Nppb, which has previously been implicated in itch, appears to act downstream of the receptor. Mice lacking Nppb scratched less and developed thinner skin in the psoriasis model.
Gpr35-deficient mice also took longer to move away from some hot surfaces. They showed no differences in tests involving cold or touch.
Potential relevance to human disease
According to the authors, GPR35 is present in human sensory neurons. In samples from two donors, all of the Nppb-expressing neurons examined also expressed GPR35.
“This study shows the importance of GPR35, as this receptor is involved in two very different diseases: autoimmune and allergic diseases,” Mishra said.
“However, in both diseases, the itch pathway uses the same receptors. This means that GPR35 is a promising therapeutic target for both diseases.”
The findings appear in the journal Communications Biology.
JJ Wheeler et al. 2026. “Metabolic sensor Gpr35 links dietary lipids to itch-mediating neural circuits.” Communications Biology 9, 1393. Read the study. doi: 10.1038/s42003-026-11087-x
Source: www.sci.news