Researchers led by Santosh Mishra have identified a neuro-metabolic circuit linking dietary linoleic acid to chronic itch. The breakdown product EKODE binds directly to GPR35 receptors on sensory neurons, triggering the release of BNP peptide to signal itch. In mouse models of psoriasis and eczema, genetic ablation or pharmacological blockage of GPR35 significantly suppressed inflammation and scratching, establishing GPR35 as a promising therapeutic target across autoimmune and allergic skin disorders.
EKODE activates GPR35 to trigger itch
- ▪Activation of GPR35 by EKODE causes sensory neurons to release the neuropeptide BNP, driving the chronic itch response.
- ▪The linoleic acid metabolite EKODE directly binds to and activates GPR35 receptors on sensory neurons in dorsal root ganglia.
GPR35 and BNP knockouts reduce psoriasis itch
- ▪BNP knockout mice subjected to the imiquimod psoriasis model display reduced itch behavior and skin inflammation.
- ▪Mice lacking the GPR35 receptor exhibit significantly reduced cutaneous inflammation and scratching behavior in the imiquimod psoriasis model.
GPR35 as a broad therapeutic target for itch
- ▪Targeting the GPR35 neuro-metabolic pathway presents a prospective therapeutic strategy for treating chronic pruritus in human and veterinary medicine.
- ▪GPR35 serves as a shared neural receptor mediating chronic itch across both autoimmune psoriasis and allergic atopic dermatitis.
- ▪Treatment with a GPR35 receptor antagonist significantly reduces the itch response in a mouse model of eczema.
Dietary linoleic acid and chronic disease risk
- ▪Linoleic acid is the most abundant polyunsaturated fatty acid present in human skin and in modern Western diets.
- ▪Overconsumption of dietary linoleic acid is linked to increased risk of chronic conditions including heart disease, diabetes, and psoriasis.
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