Research progress in neuroimmune disorders in atopic dermatitis

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease with the highest incidence in the world. The main clinical manifestations are eczema-like skin lesions, pruritus and xeroderma. Recent studies have revealed that sensory neurons in the skin lesions of AD patients can interact abnormally with keratinocytes (KC) and immune cells, leading to neuroimmune disorders. Among them, there are two types of sensory neurons involved in neuroimmune disorders, including histaminergic and non-histaminergic sensory neurons. In neuroimmune disorders, KC and immune cells activate sensory neurons to induce pruritus by secreting proinflammatory cytokines such as interleukin-4 (IL-4), IL-13, IL-31, IL-33, and thymic stromal lymphopoietin, as well as chemokines such as C-X-C motif chemokine ligand 12 (CXCL12) and CXCL10. In addition, neuropeptides such as nerve growth factor, brain-derived neurotrophic factor and artemin secreted by KC and immune cells can induce overgrowth of sensory neurons, thereby promoting neuroimmune disorders. At the same time, the excessive release of neuropeptides such as calcitonin gene-related peptide and substance P by sensory neurons can act on KC and immune cells, thereby aggravating skin inflammation. In recent years, many drugs targeting neuroimmune disorders are in preclinical studies, clinical trials and other stages, or have been marketed for the treatment of AD. Among them, our research group has found that lidocaine, a local anesthetic, can target neuroimmune disorders and relieve pruritus and skin inflammation in AD patients. At present, the role of neuroimmune disorders in AD has not been systematically discussed. Based on this, this article reviews the types of sensory neurons involved in neuroimmune disorders, the role of KC, immune cells and sensory neurons in neuroimmune disorders, as well as the therapeutic strategies targeting neuroimmune disorders.

Keywords

• atopic dermatitis (ad)
• neuroimmune
• sensory neuron
• immune cell
• keratinocyte (kc)