Sympathetic nerve aggravates autoimmune skin disease via NE–adrenergic receptor axis: Neuroimmune cross-talk insights from vitiligo

The dysregulation of cross-talk between the sympathetic nervous system (SNS) and the immune system is closely linked to the development of autoimmune diseases. This study used vitiligo as a model to elucidate the role of the SNS in autoimmune skin diseases. Evidence from clinical and animal studies confirmed abnormal activation of the SNS in vitiligo. Chemical sympathectomy improved the disease phenotype, reduced pathogenic cytokine levels, and inhibited the infiltration and effector functions of CD8⁺ T cells. Mechanistic investigations showed that norepinephrine (NE) released by the SNS interacts with adrenergic receptors to drive fibroblasts and keratinocytes to secrete chemokines CXCL9/10 and inflammatory mediators IL-6/15, establishing a pathological immune microenvironment conducive to the recruitment and activation of CD8⁺ T cells. Adrenergic receptor antagonists could reverse this abnormal immune microenvironment. This study elucidated the pathogenic mechanism of the SNS in vitiligo via the NE-adrenergic receptor-fibroblast/keratinocyte pathway, providing a theoretical foundation for neuroimmune therapy.