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• Regnase-1 degrades pro-inflammatory cytokine mRNAs, maintaining immune balance in skin cells and preventing excessive inflammation. • Regnase-1 deficiency contributes to atopic dermatitis and psoriasis, influencing Th2 and Th17 pathways. • Regnase-1 acts as a tumor suppressor in melanoma but promotes squamous cell carcinoma when deficient. • Regnase-1-targeted therapies reduce inflammation and disease severity in animal models. • Regnase-1 is a promising target for treating inflammatory skin diseases by modulating immune pathways. 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. 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. 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.
Kim et al. (Tue,) studied this question.