TRPA1 as the Intersection of Sensory Perception, Innate Immunity, and Adaptive Immune Regulation in Cutaneous...

Transient receptor potential ankyrin 1 (TRPA1) is a polymodal ion channel best known for its role in nociception and environmental sensing. However, TRPA1 is now recognized to be expressed in several non-neuronal cell types, including keratinocytes and immune cells, suggesting a broader role in the regulation of cutaneous immune responses. This comprehensive review examines the current evidence linking TRPA1 to cutaneous immunity under both physiological and pathological conditions with particular focus on inflammatory skin disorders such as atopic dermatitis, allergic contact dermatitis and psoriasis. The available literature reveals a complex picture in which TRPA1 can either amplify or restrain immune responses depending on the cellular context, disease setting, and nature of the triggering stimulus. Moreover, TRPA1 is dynamically regulated by cytokines, oxidative stress, and tissue-derived signals. Discrepancies among experimental studies further highlight the impact of species-specific differences, disease models, and methodological approaches on the interpretation of TRPA1 function. Through a critical appraisal of the existing literature, this review seeks to disentangle the complex and sometimes contradictory evidence surrounding TRPA1 in cutaneous immunity, identifying emerging concepts, highlighting unresolved issues, and providing a clearer framework for understanding TRPA1 biology and guiding future research.