Neuronal Regulation of Inflammation in Atopic Dermatitis

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by impaired barrier function, immune dysregulation, and severe pruritus. Recent studies have highlighted the pivotal role of neuronal regulation in modulating inflammation within the skin. Neuroimmune interactions, particularly between sensory neurons and immune cells, such as macrophages and mast cells, contribute significantly to the pathophysiology of AD. Additionally, neuropeptides and neurotrophins, including substance P and neurotrophin-4, have been implicated in amplifying inflammation and promoting skin barrier dysfunction. SUMMARY: This review explores the complex mechanisms underlying neuronal regulation of inflammation in AD, emphasizing the bidirectional communication between the nervous and immune systems. The review further emphasizes that pruritus is a primary driver of disease burden and should be a co-primary therapeutic target alongside inflammation control. The review also discusses emerging therapeutic strategies targeting neuroimmune circuits, including biologic agents against pruritogenic cytokines, kinase inhibitors, and neuropeptide antagonists. Finally, we address the role of adjunctive topical strategies, such as moisturizers containing topical anesthetics and calming botanical agents, which act to dampen neuronal excitability and support barrier repair. KEY MESSAGES: Collectively, these approaches offer novel and multifaceted strategies for managing both pruritus and inflammation in AD. Understanding these neuroimmune pathways is crucial for developing more effective, targeted treatments for this debilitating condition.