[Adipose-derived stem cell exosomes promote regulatory T cell-mediated immunosuppression in a murine model of allergic rhinitis].

Objective: To compare different administration routes of adipose-derived stem cell exosomes (ADSC-Exos) in mice with allergic rhinitis (AR) and, after identifying the optimal route, as well as to evaluate the effects of different ADSC-Exo concentrations on regulatory T cell (Treg)-mediated immunosuppression. Methods: ADSC-Exos labeled with the fluorescent dye DiR were administered to AR mice via intranasal microneedle injection (n=7), tail-vein injection (n=7), or intranasal instillation (n=7). The distribution and retention of ADSC-Exos at different time points were monitored using a small-animal in vivo imaging system. Serum levels of interleukin (IL)-4, IL-5, IL-10, and transforming growth factor-β (TGF-β) were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of IL-4, IL-5, and forkhead box P3 (Foxp3) in the nasal mucosa were determined using reverse transcription quantitative polymerase chain reaction (RT-qPCR). The proportion of Treg cells and the mean fluorescence intensity of Foxp3 in peripheral blood were assessed by flow cytometry. Histopathological changes in the nasal mucosa were evaluated using hematoxylin and eosin (H&E) staining. After the optimal administration route had been identified, the therapeutic effects of ADSC-Exos at concentrations of 10, 50, and 100 μg/ml were further compared. Results: Among the three administration routes, intranasal microneedle injection resulted in the strongest fluorescence signal in the nasal region and the longest retention time. Intranasal microneedle injection was also superior to the other routes in alleviating symptoms, regulating inflammatory cytokine levels and related gene expression, increasing the proportion of Treg cells and enhancing their suppressive function, and improving nasal mucosal histopathological changes. The 100 μg/ml group (the high-concentration group) exhibited the most pronounced immunomodulatory effects, including the greatest improvement in symptoms, greater reductions in proinflammatory cytokine levels, and marked increases in anti-inflammatory cytokine levels (all P<0.05). In addition, Foxp3 mRNA expression was significantly upregulated, the proportion of Treg cells was significantly increased, their suppressive function was enhanced, and eosinophilic infiltration was reduced. Conclusion: Intranasal microneedle administration of ADSC-Exos at 100 μg/ml can effectively enhance Treg cell-mediated immunosuppression and ameliorate immune imbalance in AR mice, providing experimental evidence for the clinical application of ADSC-Exos in the treatment of AR.