A DMV–VAGUS–SPLEEN NEUROIMMUNE CIRCUIT MEDIATES LI11 ACUPOINT-DRIVEN SUPPRESSION OF ATOPIC DERMATITIS

Atopic dermatitis (AD) is a chronic pruritic dermatosis in which barrier disruption and type 2 inflammation are reinforced by neuroimmune signaling, yet the underlying circuits remain underdeveloped. We investigated whether chemogenetic activation of LI11 (曲池) mitigates MC903-induced AD by engaging an LI11–vagus–spleen axis. To achieve circuit-precise control, we delivered AAVretro-hSyn-hM3Dq-mCherry into LI11 and activated DREADDs with clozapine-N-oxide. In MC903-treated C57BL/6 mice, chemogenetic activation of LI11 reduced scratching behavior, composite dermatitis scores, epidermal thickening, and mast cell/eosinophil infiltration. At the molecular level, chemogenetic activation of LI11 suppressed lesional Th1/Th2-associated transcripts consistent with reduced inflammatory drive. In parallel, splenic immunity was reprogrammed toward regulation, characterized by expansion of CD4⁺CD25⁺Foxp3⁺ regulatory T cells and concomitant attenuation of Th1/Th2 and B cell–related signatures. Central engagement was supported by robust c-Fos induction in the dorsal motor nucleus of the vagus (DMV), and splenic Fluoro-Gold retrograde tracing identified DMV neurons recruited during LI11 activation, implicating a vagal efferent hub. Functional necessity was demonstrated by loss of behavioral, histologic, and immunologic benefit after subdiaphragmatic vagotomy or splenectomy. Finally, projection-specific manipulation using spleen AAVretro-Cre and DMV Cre-dependent hM3Dq/hM4Di provided causal evidence that DMV→spleen neurons are sufficient and required for disease control. Collectively, these findings define a LI11→vagus→spleen circuit through which acupoint stimulation reprograms splenic immunity and suppresses pruritic skin inflammation, providing a mechanistic basis for circuit-guided neuromodulatory therapy in AD.