Distinct Neuroimmune Regulatory Networks in DRG Neurons of Atopic Dermatitis and Psoriasis Mouse Models 2861

Abstract Description Atopic dermatitis and psoriasis are prevalent inflammatory skin diseases with distinct immunological profiles. These conditions impact dorsal root ganglion (DRG) neurons, leading to neuronal sensitization, which in turn sustains inflammation, forming a bidirectional interaction. However, the differences in DRG neurons between atopic dermatitis and psoriasis remain unexplored. We employed single-cell RNA sequencing (scRNA-seq) to analyze inflammatory skin disease models, focusing on DRG neurons to characterize gene regulation under inflammatory conditions. Additionally, chromatin accessibility was assessed through ATAC-seq in highly purified small nociceptor neurons across these models. In parallel, skin scRNA-seq data were used to infer cell-cell interactions, linking skin ligands to DRG receptors and activated transcription factors in neurons. Our integrative analysis defines the key differential regulatory landscape between atopic dermatitis and psoriasis models. We also identified potential pathways involving skin ligands, DRG receptors, and specific transcription factors unique to each disease. These findings establish a foundation for understanding of gene regulatory landscape within DRG neurons. By distinguishing unique regulatory networks in DRG neurons, we provide insights for precision treatments to modulate neuronal sensitization and disrupt chronic inflammation, advancing therapeutic approaches for pathological neuro-immune interaction in inflammatory skin diseases. Funding Sources This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIT) (NRF-2023R1A2C1005804, RS-2024-00408822). Support was also provided by a grant from the MD-PhD/Medical Scientist Training Program, administered by the Korea Health Industry Development Institute (KHIDI) and funded by the Ministry of Health & Welfare of the Republic of Korea. Topic Categories Neuroimmunology (NEUR)