Anti-Interleukin-9 Antibody Increases the Effect of Allergen-Specific Immunotherapy in Murine Allergic Rhinitis.
10.4168/aair.2017.9.3.237
- Author:
Ji Hyeon SHIN
1
;
Do Hyun KIM
;
Boo Young KIM
;
Sung Won KIM
;
Se Hwan HWANG
;
Joohyung LEE
;
Soo Whan KIM
Author Information
1. Department of Otolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea. kshent@catholic.ac.kr
- Publication Type:Original Article
- Keywords:
Allergic rhinitis;
interleukin-9;
mouse;
oral tolerance;
regulatory T cells
- MeSH:
Animals;
Blotting, Western;
Cytokines;
Desensitization, Immunologic;
Eosinophils;
Flow Cytometry;
Humans;
Immunoglobulin E;
Immunoglobulins;
Immunotherapy*;
Inflammation;
Interleukin-10;
Interleukin-9;
Interleukins;
Mice;
Nasal Mucosa;
Ovalbumin;
Ovum;
Real-Time Polymerase Chain Reaction;
Rhinitis, Allergic*;
RNA, Messenger;
Spleen;
T-Lymphocytes;
T-Lymphocytes, Regulatory;
Th17 Cells;
Transcription Factors
- From:Allergy, Asthma & Immunology Research
2017;9(3):237-246
- CountryRepublic of Korea
- Language:English
-
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.
