The pathogenesis of atopic dermatitis (AD) is influenced by immune dysregulation, barrier dysfunction, and pruritus. Various immune cells, including Th2 cells, type 2 innate lymphoid cells (ILC2s), and basophils, produce Th2 cytokines (IL-4, IL-5, IL-13, IL-31) in lesional skin. Alarmins like TSLP, IL-25, and IL-33, from keratinocytes, amplify type 2 inflammation. In chronic AD, Th22 and Th17 cells further suppress filaggrin expression, worsening barrier function. Treatments like dupilumab (IL-4/IL-13 inhibitor) and nemolizumab (IL-31RA inhibitor) show efficacy in moderate-to-severe AD.

The complexity of AD pathogenesis is underscored by the differential roles of cytokines in humans and mouse models. Cytokines such as IL-4, IL-13, IL-31, and IL-22 are critical therapeutic targets, with treatments like dupilumab and fezakinumab showing effectiveness in clinical trials. In contrast, therapies targeting IL-33, TSLP, IL-1α, IL-5, and IL-17 have not demonstrated sufficient efficacy in human trials. The disparity between murine models and human AD highlights the need for further research to understand the specific roles of cytokines and develop effective treatments for AD.

Reference: Yamamura Y, Nakashima C, Otsuka A. Interplay of cytokines in the pathophysiology of atopic dermatitis: insights from Murin models and human. Front Med (Lausanne). 2024;11:1342176. doi: 10.3389/fmed.2024.1342176.