Anti-Interleukin-9 Antibody Increases the Effect of Allergen-Specific Immunotherapy in Murine Allergic Rhinitis

Content Provider	Semantic Scholar
Author	Shin, Ji-Hyeon Kim, Do Hyun Kim, Boo Young Kim, Sung Won Hwang, Se Hwan Lee, Joohyung Kim, Soo Whan
Copyright Year	2017
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.
Starting Page	237
Ending Page	246
Page Count	10
File Format	PDF HTM / HTML
PubMed reference number	28293930v1
Alternate Webpage(s)	https://doi.org/10.4168/aair.2017.9.3.237
DOI	10.4168/aair.2017.9.3.237
Journal	Allergy, asthma & immunology research
Volume Number	9
Language	English
Access Restriction	Open
Subject Keyword	Allergens Allergic rhinitis (disorder) Drug Allergy Flow Cytometry GATA3 protein, human Immunoglobulin E Immunotherapy Interleukins Ovalbumin Patients Polymerase Chain Reaction Regulatory T-Lymphocytes SPI1 gene Sensitization (observable entity) Spleen Tissue Structure of mucous membrane of nose T-helper cell type 2 TRANSCRIPTION FACTOR Western Blotting eosinophil oral tolerance
Content Type	Text
Resource Type	Article