title: Tumor necrosis factor-related apoptosis-inducing ligand mediates the resolution of allergic airway inflammation induced by chronic allergen inhalation.
abstract: Allergic asthma can vanish over time either spontaneously or induced by allergen-specific immunotherapy. In mice with established airway allergic inflammation, chronic intranasal (IN) allergen challenges decreases progressively airway allergic inflammation. Here we compared the contribution of different regulatory pathways that could be associated with this phenomenon, known as local inhalational tolerance. We found that inhalational tolerance was not associated with increased number of regulatory T cells or suppressive cytokines. Instead, it was associated with increased apoptosis of airway inflammatory leukocytes revealed by annexin-V staining and the expression of apical caspase 8 and effector caspase 3. Also, the transition from acute to chronic phase was associated with a shift in the expression of pro-allergic to pro-apoptotic molecules. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was found to be a key molecule in mediating resolution of allergic inflammation because anti-TRAIL treatment blocked apoptosis and increased the infiltration of T helper type 2 (Th2) cells and eosinophils. Notably, repeated IN treatment with recombinant TRAIL in established airway allergic inflammation augmented leukocyte apoptosis and decreased the frequency of interleukin-5-producing Th2 cells and eosinophils to airways. Our data indicate that TRAIL signaling is sufficient for downmodulation of allergic airway disease, suggesting a potential therapeutic use of TRAIL for asthma treatment.
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: L
authors.initials: L
authors.lastname: Faustino
authors.affiliation: Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: D M
authors.initials: DM
authors.lastname: Fonseca
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: E B
authors.initials: EB
authors.lastname: Florsheim
authors.affiliation: Department of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: R R
authors.initials: RR
authors.lastname: Resende
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: A P
authors.initials: AP
authors.lastname: Lepique
authors.affiliation: Laboratory of Immunopathology, Butantan Institute, São Paulo, Brazil.
authors.forename: E
authors.initials: E
authors.lastname: Faquim-Mauro
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: E
authors.initials: E
authors.lastname: Gomes
authors.affiliation: Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: J S
authors.initials: JS
authors.lastname: Silva
authors.affiliation: Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yagita
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: M
authors.initials: M
authors.lastname: Russo
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D002908:Chronic Disease; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D011994:Recombinant Proteins / Q000235:genetics; D012130:Respiratory Hypersensitivity / Q000188:drug therapy / Q000276:immunology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000485:Allergens; D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; D053148:Caspase 3; D053181:Caspase 8