Targeting type 2 inflammation in dermatology: mechanisms and clinical implications

Type 2 inflammation is a fundamental immunologic pathway underlying a growing spectrum of dermatologic diseases. While classically associated with atopic dermatitis, type 2 immune responses are increasingly recognized as key contributors to prurigo nodularis, chronic spontaneous urticaria, bullous pemphigoid, lichen simplex chronicus, and other chronic pruritic disorders. Barrier disruption and epithelial injury initiate the release of alarmins, including thymic stromal lymphopoietin (TSLP), interleukin (IL)-33, and IL-25, which activate innate and adaptive immune pathways that promote type 2 inflammation. Subsequent production of effector mediators such as IL-4, IL-13, IL-5, IL-31, immunoglobulin E (IgE), and periostin drives barrier dysfunction, immune cell recruitment, tissue remodeling, and chronic pruritus. Increasing evidence further highlights the importance of neuroimmune crosstalk, with direct interactions between immune cells, cytokines, and sensory neurons contributing to itch sensitization and disease persistence. The clinical success of biologic therapies targeting IL-4/IL-13, IgE, and IL-31 signaling has provided powerful functional validation of these pathogenic pathways and has transformed the management of multiple inflammatory skin diseases. In this review, we summarize the molecular and cellular mechanisms underlying type 2 inflammation in the skin, discuss its role across diverse dermatologic conditions, and highlight emerging concepts in disease heterogeneity, neuroimmune signaling, and precision medicine. Collectively, these findings support type 2 inflammation as a unifying immunologic framework and therapeutically actionable target across dermatology.