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<p>The skin is a highly innervated and immunologically active barrier organ, where neuro-immune interactions critically shape both physiological homeostasis and disease progression. Growing evidence indicates that bidirectional crosstalk between the nervous and immune systems is not only central to the pathogenesis of allergic skin diseases but also represents an emerging frontier for therapeutic innovation. In this review, we systematically examine atopic dermatitis (AD), contact dermatitis (CD), and urticaria, integrating insights into peripheral pathways-mediated by sensory neurons, cytokine networks, and immune cells-and central mechanisms involving the hypothalamic-pituitary-adrenal axis and higher neural circuits. By contrasting shared and disease-specific neuro-immune signatures, we highlight how these mechanisms underlie distinct inflammatory phenotypes and clinical manifestations. We further evaluate current and investigational therapies, including biologics and small molecules that target neuro-immune signaling, and discuss their translational significance. Looking ahead, we identify unresolved questions and propose future directions aimed at leveraging neuro-immune mechanisms to advance precision diagnosis and personalized interventions in allergic skin diseases.</p> Graphical Abstract <p> The main pathological mechanisms and key interaction pathways between the nervous and immune systems that mediate and regulate inflammation in cutaneous allergic diseases are illustrated in the graphical abstract, with the principal mechanisms of neurogenic inflammation and the itch-scratch cycle highlighted by thick arrows.</p> <p></p>

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Pathophysiologic Mechanisms and Targeted Treatments Associated with the Nervous System in Cutaneous Allergic Diseases

  • 期刊论文

  • 发表日期：

    2025年12月17日

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  • Hantian Zhang,
  • Weiyi Xiang,
  • Yi Tong,
  • Xian Jiang,
  • Linghong Guo

摘要

The skin is a highly innervated and immunologically active barrier organ, where neuro-immune interactions critically shape both physiological homeostasis and disease progression. Growing evidence indicates that bidirectional crosstalk between the nervous and immune systems is not only central to the pathogenesis of allergic skin diseases but also represents an emerging frontier for therapeutic innovation. In this review, we systematically examine atopic dermatitis (AD), contact dermatitis (CD), and urticaria, integrating insights into peripheral pathways-mediated by sensory neurons, cytokine networks, and immune cells-and central mechanisms involving the hypothalamic-pituitary-adrenal axis and higher neural circuits. By contrasting shared and disease-specific neuro-immune signatures, we highlight how these mechanisms underlie distinct inflammatory phenotypes and clinical manifestations. We further evaluate current and investigational therapies, including biologics and small molecules that target neuro-immune signaling, and discuss their translational significance. Looking ahead, we identify unresolved questions and propose future directions aimed at leveraging neuro-immune mechanisms to advance precision diagnosis and personalized interventions in allergic skin diseases.

Graphical Abstract

The main pathological mechanisms and key interaction pathways between the nervous and immune systems that mediate and regulate inflammation in cutaneous allergic diseases are illustrated in the graphical abstract, with the principal mechanisms of neurogenic inflammation and the itch-scratch cycle highlighted by thick arrows.