Artemisia pollen-induced allergic rhinitis in mice: multi-omics dissection of local and systemic molecular alterations.

BACKGROUND: Mugwort (Artemisia vulgaris) is a predominant aeroallergen for allergic rhinitis (AR) in northern China. However, the molecular changes linking local nasal mucosal inflammation with systemic alterations remain incompletely understood. This study aimed to explore the cross-level regulatory network in a mouse model of mugwort-induced AR by combining nasal mucosal transcriptomics and serum metabolomics.

METHODS: BALB/c mice were sensitized with mugwort extract and then challenged intranasally to establish an AR model. Nasal mucosal tissues were collected for RNA sequencing, and serum samples from the same cohort were subjected to non-targeted metabolomic analysis. Transcription factor (TF)-associated analysis, pathway enrichment analysis, and integrative multi-omics analysis were used to identify candidate regulatory factors and pathways involved in mugwort-induced allergic inflammation. Targeted validation of arginine-related changes was performed by measuring serum Arg1 and L-arginine levels, followed by ARG2 knockdown analysis in BEAS-2B epithelial cells after mugwort extract stimulation.

RESULTS: Transcriptomic analysis revealed a clear Th2-type immune response in the model group, with significant upregulation of Il13, Arg1, Ccl24 and Il6. In addition, many downregulated genes were enriched in pathways related to ciliary function and epithelial differentiation, accompanied by suppression of structural genes such as Krt25 and Krt71. Gene set enrichment and TF-associated analyses further highlighted cytokine-mediated signaling and potential upstream regulators, including Fos, Batf, and Mafb. Serum metabolomics showed increased 1-methylhistamine and enrichment of arachidonic acid metabolism in mugwort-treated mice. Integrated analysis of the two omics datasets further pointed to arginine-related metabolism as a shared altered pathway. Consistently, targeted assays showed increased serum Arg1 levels and decreased serum L-arginine concentrations in the mugwort group. In BEAS-2B cells, ARG2 knockdown attenuated the induction of IL6 and CCL26 after mugwort extract stimulation.

CONCLUSION: Together, our findings indicate that mugwort-induced AR is accompanied by coordinated local and systemic changes, including immune activation, epithelial/ciliary dysfunction, and serum metabolic remodeling. The arginine-related alterations supported by both omics analysis and targeted validation provide a potential link between nasal mucosal inflammation and systemic metabolic changes in mugwort allergy.