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Anti-Interleukin-9 Antibody Increases the Effect of Allergen-Specific Immunotherapy in Murine Allergic Rhinitis
Article in En | WPRIM | ID: wpr-179284
Responsible library: WPRO
ABSTRACT
PURPOSE: Interleukin (IL)-9 induces allergic responses; however, the roles of anti-IL-9 antibody in the induction of tolerance remain unclear. This study investigated the effects of anti-IL-9 antibody on oral tolerance (OT) in a mouse model of allergic rhinitis (AR). METHODS: BALB/c mice were divided into 4 groups: the control, AR, OT, and OT with anti-IL-9 antibody (OT+IL9AB) groups. Ovalbumin (OVA) was used for sensitization and challenge. Mice in the OT and OT+IL9AB groups were fed OVA for immunotherapy. During immunotherapy, OT+IL9AB mice were injected with anti-IL-9 antibody. Allergic symptoms, tissue eosinophil counts, and serum OVA-specific immunoglobulin E (IgE) were measured. The mRNA expressions of cytokines and transcription factors of T cells of nasal mucosa were determined by real-time polymerase chain reaction (PCR). The protein levels of GATA3, ROR-γt, and Foxp3 in nasal mucosa were determined by Western blot. CD4⁺CD25⁺Foxp3⁺ T cells in the spleen were analyzed by flow cytometry. RESULTS: Administration of anti-IL-9 antibody decreased allergic symptoms, OVA-specific IgE levels, and eosinophil counts. In addition, it inhibited T-helper (Th) 2 responses, but had no effect on Th1 responses. Protein levels of ROR-γt and mRNA levels of PU.1 and ROR-γt were reduced by anti-IL-9 antibody. Anti-IL-9 antibody increased Foxp3 and IL-10 mRNA expression, Foxp3 protein, and induction of CD4⁺CD25⁺Foxp3⁺ T cells. CONCLUSIONS: Anti-IL-9 antibody decreased allergic inflammation through suppression of Th2 and Th17 cells. Anti-IL-9 antibody enhanced the tolerogenic effects of regulatory T cells. These results suggest that anti-IL-9 antibody might represent a potential therapeutic agent for allergen immunotherapy in patients with uncontrolled allergic airway disease.
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Full text: 1 Index: WPRIM Main subject: Ovum / Spleen / Transcription Factors / Immunoglobulin E / Immunoglobulins / RNA, Messenger / T-Lymphocytes / Ovalbumin / Blotting, Western / Cytokines Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: Allergy, Asthma & Immunology Research Year: 2017 Type: Article
Full text: 1 Index: WPRIM Main subject: Ovum / Spleen / Transcription Factors / Immunoglobulin E / Immunoglobulins / RNA, Messenger / T-Lymphocytes / Ovalbumin / Blotting, Western / Cytokines Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: Allergy, Asthma & Immunology Research Year: 2017 Type: Article