title: Beneficial effects of Galectin-9 on allergen-specific sublingual immunotherapy in a Dermatophagoides farinae-induced mouse model of chronic asthma.
abstract: BACKGROUND
  Allergen-specific sublingual immunotherapy is a potential disease-modifying treatment for allergic asthma. Galectin-9 (Gal-9), a β-galactoside-binding protein with various biologic effects, acts as an immunomodulator in excessive immunologic reactions by expanding regulatory T cells (Treg) and enhancing transforming growth factor (TGF)-β signaling. We investigated the efficacy of sublingually administered Gal-9 as an adjuvant to a specific allergen in a Dermatophagoides farinae (Df)-induced mouse model of chronic asthma.
  
  
  METHODS
  BALB/c mice were intranasally sensitized with Df extract 5 days/week for 5 weeks, and then sublingual Df-allergen extract for 2 weeks (5 days/week). Three days after the final sublingual treatment, mice were intranasally challenged with Df extract. The early asthmatic response (EAR) was evaluated 5 min after the last Df challenge. Airway hyperresponsiveness (AHR) was assayed and bronchoalveolar lavage (BAL) was performed 24 h after the last allergen challenge. Serum IgE and cytokine levels, and number of inflammatory cells in the BAL fluid (BALF) were analyzed.
  
  
  RESULTS
  Sublingual Df treatment in the presence of Gal-9, but not alone, significantly reduced AHR; EAR; number of eosinophils and interleukin-13 in the BALF; and serum IgE levels. BALF TGF-β1 levels were significantly increased in the presence of Gal-9 compared with Df alone. Treg depletion blocked the inhibitory effects of Gal-9 on the EAR, AHR, eosinophilic airway inflammation, and Df-specific serum IgE levels, and suppressed BALF TGF-β1 levels.
  
  
  CONCLUSIONS
  Gal-9 exhibited beneficial effects of sublingual Df allergen-specific immunotherapy in a Df-induced mouse model of chronic asthma, possibly by Gal-9-induced TGF-β1 production in the lung.
authors.affiliation: Department of Respiratory Medicine, Kawasaki Medical School, Okayama, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Department of Respiratory Medicine, Kawasaki Medical School, Okayama, Japan. Electronic address: kshigeki@med.kawasaki-m.ac.jp.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Katoh
authors.affiliation: Department of Respiratory Medicine, Kawasaki Medical School, Okayama, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shimizu
authors.affiliation: Research Laboratories, Torii Pharmaceutical Co., Ltd., Chiba, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Hasegawa
authors.affiliation: Research Laboratories, Torii Pharmaceutical Co., Ltd., Chiba, Japan.
authors.forename: Katsuyo
authors.initials: K
authors.lastname: Ohashi-Doi
authors.affiliation: Department of Respiratory Medicine, Kawasaki Medical School, Okayama, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Oka
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology*; D001249:Asthma / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D016207:Cytokines / Q000378:metabolism; D040001:Dermatophagoides farinae / Q000276:immunology*; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D037161:Galectins / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D008212:Lymphocyte Depletion; D051379:Mice; D063729:Sublingual Immunotherapy; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D039741:Antigens, Dermatophagoides; D016207:Cytokines; D037161:Galectins; C508186:galectin 9, mouse; D007073:Immunoglobulin E
keywords: Galectin-9; Mite allergen; Mouse; SLIT; TGF-β1