Targeting the JAK/STAT pathway in atopic dermatitis

Atopic dermatitis (AD) is a chronic, inflammatory skin disorder characterized by immune dysregulation, skin barrier dysfunction, and pruritus. Central to its pathogenesis is the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway, which mediates cytokine responses-including interleukin (IL)-4, IL-13, IL-31, and thymic stromal lymphopoietin-that drive T-helper 2-skewed inflammation and epidermal barrier impairment. In recent years, the therapeutic landscape of AD has been transformed by the development of JAK inhibitors, offering both systemic and topical treatment options for patients unresponsive to conventional therapies. This narrative review provides a comprehensive overview of the JAK/STAT pathway's biological role in AD, including its regulation of immune responses and skin inflammation. We summarize current JAK inhibition therapies under clinical use or investigation, compare their efficacy and safety profiles, and examine unresolved controversies surrounding long-term outcomes and adverse effects. Furthermore, we explore future innovations in JAK/STAT research, including precision medicine approaches, third-generation allosteric inhibitors, microbiome-informed strategies, and advanced drug delivery technologies. Collectively, understanding and refining JAK/STAT-targeted therapy hold great promise for individualized, safe, and effective management of AD.