A Preliminary Investigation of the Differences in Immune Responses in Different Strains of Mice with Localized Allergic Rhinitis Tolerance Models

Abstract Background： BALB/c and C57BL/6 are two common mice strains for the study of allergic rhinitis (AR). We previously found that both mice differed in symptoms and immune phenotypes in the local allergy models.This study aimed to systematically compare the immune differences between the two mice in a local tolerance model and explore the underlying mechanisms. Methods: We used ovalbumin (OVA) as a topical nasal drop for 15 weeks in BALB/c and C57BL/6 mice. Allergic symptoms were recorded. Serum-specific OVA antibodies (IgE, IgG1, IgG2a) and cytokines (IL-4, IL-10, and IFN-γ) in the spleen cell culture supernatants were tested. The expression of eosinophils, goblet cells, TGF-β, IL-10, eotaxin, and RNA-seq on the nasal mucosa was examined. Results: Nasal symptoms of BALB/c worsened first and then relieved, whereas C57BL/6 showed continuously worsened symptoms. The serum antibodies levels in BALB/c increased over time. IgE and IgG1 levels in C57BL/6 showed a trend similar to that of BALB/c, while IgG2a levels did not increase throughout the course. IL-4 first increased and then decreased, while IL-10 remained increased in BALB/c, whereasC57BL/6 showed no significant changes. In BALB/c, the expression of eosinophils and eotaxin in the nasal mucosa increased to a certain extent and remained unchanged, whereas TGF-β and IL-10 expression was upregulated. In C57BL/6, the expression of eosinophils and eotaxin was higher than that in BALB/c at the 15th week. The RNA-sequencing results showed that gene expression in BALB/c was upregulated in biological processes, the tolerance and negative regulatory pathway at the 15th week. Gene expression in C57BL/6 is upregulated in cell synthesis- and secretion-related pathways. Conclusion: Local tolerance and systemic sensitisation was successfully induced in BALB/c by long-term stimulation with OVA. However, local tolerance could not be induced in C57BL/6 . The normal function of T regulatory cells is key to local tolerance.