A recent study has uncovered a significant link between a breakdown product of dietary fat and the itch associated with psoriasis. Researchers from North Carolina State University discovered that a derivative of linoleic acid, a common fatty acid found in various foods, can bind to a receptor that plays a critical role in psoriatic itch and inflammation. By inhibiting this receptor, the team observed a decrease in itch levels in a mouse model, suggesting a potential dietary influence on chronic itch triggers.
Linoleic acid is prevalent in many foods, such as nuts, seeds, and vegetable oils. While it is essential for human health in moderate amounts, excessive intake has been linked to various health issues, including heart disease and diabetes. Santosh Mishra, a professor in NC State’s College of Veterinary Medicine and the study’s lead author, noted, “We also know that certain polyunsaturated fat-derived molecules are associated with itch, and that linoleic acid is the most abundant polyunsaturated fat found in both skin and western diets.”
Research Focus on EKODE
The team’s research centered on a specific linoleic acid derivative named 9-keto-12,13-epoxy octadecenoic acid (EKODE), which has been identified in elevated levels in psoriatic lesions. EKODE has also been shown to trigger itching in mice, prompting the researchers to investigate its mechanisms further.
In both humans and rodents, sensory neurons within the dorsal root ganglia (DRG) express ion channels like TRPV1 and TRPA1, which are involved in mediating pain and itch sensations. By examining EKODE’s effects on mouse DRG and cultured human neurons, the researchers identified a signaling pathway that links EKODE from the skin to the spinal cord through a neuropeptide called BNP, which is specifically associated with itch responses.
Findings on GPR35 Receptor
The study revealed that EKODE activates a receptor known as GPR35 on sensory neurons, leading to the release of BNP and the initiation of itching. The researchers confirmed the presence of GPR35 on both TRPV1 and TRPA1 sensory neurons in rodent and human DRG neurons.
To further explore this pathway, the researchers utilized a mouse model of psoriasis. They compared the itch response to EKODE in mice with and without GPR35 receptors and found that the GPR35 knockout mice exhibited reduced inflammation and itch compared to those with the receptor. A similar reduction in itch and inflammation was observed in BNP knockout mice.
Potential for Future Therapies
Additionally, treatment with a GPR35 blocker in a mouse model of eczema resulted in a significant decrease in the itch response. The researchers are optimistic that their findings could lead to new treatments for psoriasis and other chronic itch conditions, including atopic dermatitis.
Mishra emphasized the significance of GPR35, stating that the receptor is involved in two distinct conditions—autoimmune and allergic—highlighting its potential as a therapeutic target for both. The study has been published in the journal Communications Biology, with substantial support from the National Institutes of Health. Joshua Wheeler, a postdoctoral researcher at NC State, served as the lead author, alongside various contributors from multiple institutions.
Source: NC State University
