Spatial neuro-immune networks of dorsal root ganglion and skin in an MC903-induced atopic dermatitis-like mouse model

초록

Chronic pruritus is a defining feature of atopic dermatitis, yet the spatial organization of neuroimmune interactions across sensory ganglia and skin remains incompletely understood. This study aimed to construct a spatial atlas of the mouse dorsal root ganglion (DRG) and skin and to define transcriptomic alterations associated with itch using a topical vitamin D analog (MC903)-induced atopic dermatitis (AD)—like mouse model. High-plex in situ spatial transcriptomic profiling was performed with a targeted gene panel on DRG and skin tissues from wild-type and MC903-induced mice, followed by cell-type annotation, differential expression, module-based and gene set enrichment analyses, and pseudo-bulk comparisons. Distinct neuronal, glial, stromal, vascular, and immune populations were resolved in the DRG, while major epithelial, mesenchymal, and immune compartments were identified in skin. Sensory neuronal subtypes, including neuronal pentraxin—defined populations, exhibited spatially organized distributions within the ganglion. In MC903-induced mice, DRG neurons exhibited upregulation of type 2 cytokine receptor genes and interleukin-17 receptor—associated signaling components, with concordant changes observed in satellite glial cells and fibroblasts, indicating coordinated immune-sensing reprogramming. In the skin, keratinocytes showed transcriptional programs related to proliferation and differentiation, while fibroblasts and immune cells demonstrated inflammatory and immune-modulatory reprogramming, including enrichment of innate immune pathways such as phagocytosis and interleukin-6—associated JAK—STAT signaling. Together, these findings define a spatially resolved neuron—skin atlas and identify coordinated neuroimmune transcriptional adaptations across sensory ganglia and skin, providing mechanistic insight into neuroimmune networks underlying AD—associated itch.