TRPA1 ion channel activation in psoriatic human skin

Psoriasis is a chronic, relapsing immune-mediated inflammatory skin disease, affecting 2-3% of the population. We have previously found that Transient Receptor Potential Ankyrin 1 (TRPA1) ion channel plays protective role in the formation of psoriasiform skin reactions. Here we further investigated the possible role of pharmacological activation and blockade of TRPA1 in human skin (patho)physiology. 6 mm full-thickness skin biopsies were obtained from psoriatic lesional and non-lesional skin of 4 patients with psoriasis as well as from normal skin of 4 healthy volunteers. Each biopsy was quartered: one segment was untreated, the other three were cultured either with vehicle (DMSO), TRPA1 agonist (mustard oil - MO) or TRPA1 antagonist (HC030031), respectively. Global gene expression was measured by RNA sequencing, followed by differential expression and functional enrichment analyses to identify TRPA1-modulated genes. Pre-evaluation of the data with ordination assessment showed clear cluster formation according to the treatments and the condition of the skin (healthy, non-lesional or lesional). In healthy skin TRPA1 blockade downregulated genes associated with interferon signalling, antimicrobial responses and inflammation/oxidative stress. In lesional psoriatic skin the genes of IL-4, IL-10 and IL-13 cytokine signalling-related proteins, circadian gene expression and Senescence-Associated Secretory Phenotype (SASP) genes were downregulated by MO treatment. Conclusion: The exploration of the interactions between TRPA1 and the identified signalling pathways may open new opportunities to target psoriasis, alleviating disease symptoms and optimizing the timing of therapies.