title: Therapeutic expansion of CD4+FoxP3+ regulatory T cells limits allergic airway inflammation during pulmonary fungal infection.
abstract: Allergic asthma can be frequently caused and exacerbated by sensitization to ubiquitous fungal allergens associated with pulmonary mucus production, airway hyperresponsiveness and bronchial constriction, resulting in a complex disease that is often difficult to treat. Fungal infections are frequently complicated by the development of a type 2 immune response that prevents successful elimination of the fungal pathogen. Furthermore, production of type 2 cytokines triggers allergic airway inflammation. Following intranasal infection of BALB/c mice with the fungusCryptococcus neoformans, we recently described a more pronounced type 2 immune response in the absence of regulatory T (Treg) cells. To determine whether Treg cell expansion is able to suppress type 2-related fungal allergic inflammation, we increased Treg cell numbers during pulmonaryC. neoformansinfection by administration of an interleukin (IL)-2/anti-IL-2 complex. Expansion of Treg cells resulted in reduced immunoglobulin E production and decreased allergic airway inflammation including reduced production of pulmonary mucus and type 2 cytokines as well as production of immunosuppressive cytokines such as IL-10 and transforming growth factor-β1. From our data we conclude that Treg cells and/or their suppressive mediators represent potential targets for therapeutic intervention during allergic fungal airway disease.
authors.affiliation: Institute of Immunology/Molecular Pathogenesis, Center for Biotechnology and Biomedicine, College of Veterinary Medicine, University of Leipzig, D-04103 Leipzig, Germany.
authors.forename: Bianca
authors.initials: B
authors.lastname: Schulze
authors.affiliation: Institute of Immunology/Molecular Pathogenesis, Center for Biotechnology and Biomedicine, College of Veterinary Medicine, University of Leipzig, D-04103 Leipzig, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Piehler
authors.affiliation: Institute of Immunology/Molecular Pathogenesis, Center for Biotechnology and Biomedicine, College of Veterinary Medicine, University of Leipzig, D-04103 Leipzig, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Eschke
authors.affiliation: Institute of Immunology/Molecular Pathogenesis, Center for Biotechnology and Biomedicine, College of Veterinary Medicine, University of Leipzig, D-04103 Leipzig, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Heyen
authors.affiliation: Institute of Immunology/Molecular Pathogenesis, Center for Biotechnology and Biomedicine, College of Veterinary Medicine, University of Leipzig, D-04103 Leipzig, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Protschka
authors.affiliation: Institute for Pathology, Klinikum Fulda gAG, Fulda, D-36043, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Köhler
authors.affiliation: Institute of Immunology/Molecular Pathogenesis, Center for Biotechnology and Biomedicine, College of Veterinary Medicine, University of Leipzig, D-04103 Leipzig, Germany alber@rz.uni-leipzig.de.
authors.forename: Gottfried
authors.initials: G
authors.lastname: Alber
mesh_terms: D000818:Animals; D015169:Colony Count, Microbial; D003455:Cryptococcus neoformans / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D056747:Immunomodulation; D018836:Inflammation Mediators / Q000378:metabolism; D008172:Lung Diseases, Fungal / Q000150:complications* / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D012130:Respiratory Hypersensitivity / Q000150:complications* / Q000276:immunology*; 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: D016207:Cytokines; D018836:Inflammation Mediators; D007073:Immunoglobulin E
keywords: T helper cells; fungal infection; mouse; regulatory T cells