Decoding Regnase-1′s role in skin inflammation: potential therapeutic implication for dermatological disorders

Background Regnase-1 is a multifunctional regulatory protein involved in immune modulation and inflammatory processes. As an endoribonuclease, it degrades mRNAs encoding pro-inflammatory cytokines, including IL-1β and IL-6. This makes it an essential factor in controlling immune cell function. Its role extends to various cell types, including keratinocytes and melanocytes, and it plays a pivotal part in maintaining skin homeostasis. Dysregulation of Regnase-1 has been implicated in various dermatological disorders, making it a significant target for understanding immune-related skin diseases. Aim of Review This review provides a comprehensive analysis of Regnase-1′s structure, function, and its diverse roles in skin biology. Specifically, it explores how Regnase-1 influences the pathogenesis of inflammatory skin diseases such as atopic dermatitis, psoriasis, and hidradenitis suppurativa, as well as its involvement in skin cancer development. By detailing Regnase-1′s regulatory mechanisms, the review aims to highlight its potential as a therapeutic target and emphasize the need for further research on its specific functions across different skin diseases and immune responses. Key Scientific Concepts of Review Regnase-1 plays a crucial role in maintaining skin immune homeostasis by controlling the degradation of pro-inflammatory cytokine mRNAs, such as IL-1β, IL-6, and IL-17. It regulates inflammatory pathways in keratinocytes, melanocytes, and immune cells, preventing excessive immune activation. In atopic dermatitis, Regnase-1 deficiency leads to heightened Th2 responses and increased chemokine levels, while in psoriasis, it modulates the IL-23/Th17 axis and STAT3 pathways, impacting keratinocyte proliferation and chronic inflammation. Furthermore, in cancer, Regnase-1 acts as a tumor suppressor in melanoma by inhibiting the Akt/mTOR pathway, but its deficiency can promote squamous cell carcinoma through increased COX-2 expression. These context-specific functions make Regnase-1 a promising target for therapies that could modulate multiple inflammatory pathways, either simultaneously or specifically, offering novel approaches to treat chronic inflammatory skin disorders and cancers.