Artemisia sieversiana protein can induce allergic rhinitis and subsequent immune tolerance establishment

Allergic rhinitis (AR) is a major global public health issue, with current treatments struggling to balance efficacy and safety, necessitating innovative immunotherapeutic strategies. Artemisia sieversiana (A. sieversiana), a common and potent inhalant allergen, severely impacts patients' quality of life. This study systematically investigates the role of A. sieversiana pollen protein in inducing AR and its potential for establishing immune tolerance. Protein characterization identified four core allergens-Art si 1, Art si 2, Art si 3, and Art si 7-and a specific AR mouse model was successfully established. Subsequently, a dissolvable microneedle was used as a delivery carrier for A. sieversiana protein to intervene in AR mice during the pre-seasonal (PSI) and in-seasonal (ISI) periods. Results showed that incremental micro-needle delivery significantly alleviated AR symptoms, modulated sIgE and sIgG1/sIgG2a balance, promoted regulatory T cell (Treg) differentiation, reduced pro-inflammatory cytokines IL-4, IL-5, IL-13, IL-33, and upregulated IFN-γ. Splenic transcriptomic analysis revealed that PSI can directly suppress IL-17 signaling pathway activation, while ISI modulates immunity through multiple pathways, including protein digestion and oxidative phosphorylation. Furthermore, both interventions downregulated the mRNA and protein expression levels of the key gene Gdf15, facilitating immune tolerance. In conclusion, this study provides novel strategies and theoretical foundations for the immunotherapy of AR caused by Artemisia pollen.