Role of transient receptor potential channels on pathogenesis and treatment of psoriasis

Psoriasis is a chronic inflammatory skin disease characterized primarily by hyperproliferation of keratinocytes, infiltration and activation of immune cells, including T lymphocytes and macrophages, as well as increased innervation by sensory neurons. Although several therapeutic options are available, the management of psoriasis remains unsatisfactory, with adverse effects and unmet clinical needs. In this context, channels from the Transient Receptor Potential (TRP) family, which are non-selective cation channels involved in various pathologies, have been identified as potential therapeutic targets for treating psoriasis. Growing evidence suggests the involvement of multiple TRP subtypes in the pathogenesis of psoriasis, including altered expression of vanilloid subtypes, such as TRPV1, TRPV3, TRPV4, TRPV6, the canonical TRPC6, and melastatin TRPM8 in patients. These channels are involved in processes such as keratinocyte differentiation and proliferation, immune cell activation (e.g., T cells), and sensory neuron stimulation. Although there are still few studies on the role of TRPs in the therapies currently used for psoriasis, there is evidence of the activation of TRPV1 and the TRPA1 subtypes in the adverse effects of topical pharmacotherapy and phototherapy. On the other hand, TRPV1 desensitization (usually produced by repeated treatment with the TRPV1 agonist capsaicin) can reduce the severity of psoriasis and pruritus. Thus, the pharmacological modulation of TRP channels represents a promising strategy for developing novel, efficacious, and safer therapies to treat patients with psoriasis. This review aimed to provide a comprehensive overview of the involvement of TRP channels in the pathogenesis and therapeutic approaches to psoriasis.