title: Anti-Interleukin-9 Antibody Increases the Effect of Allergen-Specific Immunotherapy in Murine Allergic Rhinitis.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Ji Hyeon
authors.initials: JH
authors.lastname: Shin
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Do Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Boo Young
authors.initials: BY
authors.lastname: Kim
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Se Hwan
authors.initials: SH
authors.lastname: Hwang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Joohyung
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea. kshent@catholic.ac.kr.
authors.forename: Soo Whan
authors.initials: SW
authors.lastname: Kim
keywords: Allergic rhinitis; interleukin-9; mouse; oral tolerance; regulatory T cells