title: IL-21 administration into the nostril alleviates murine allergic rhinitis.
abstract: Type I allergic diseases such as allergic rhinitis are caused by IgE-mediated humoral immune responses, while eosinophils also fulfill important roles in the etiology of IgE-mediated allergy. IL-21 regulates growth, differentiation, and function of T, B, and NK cells, while the production of IgE is also influenced by IL-21. In this study we examined whether IL-21 is capable of controlling IgE-mediated allergic reactions in vivo by using the allergic rhinitis mouse model that was established by repetitive sensitization and intranasal challenge with OVA. Intranasal administration with recombinant mouse IL-21 (rmIL-21) significantly reduced the number of sneezes, as well as the serum concentration of OVA-specific IgE, in comparison with that of untreated allergic mice. The rmIL-21 treatment also suppressed germline Cepsilon transcription in the nasal-associated lymphoid tissues, which may have, at least partly, resulted from the up-regulation of Bcl-6 mRNA caused by IL-21. Local expression of IL-4, IL-5, and IL-13 was also inhibited by the intranasal cytokine therapy whereas, in contrast, the expression of endogenous IL-21 mRNA was induced by exogenous rmIL-21. Moreover, IL-21 acted on nasal fibroblasts to inhibit production of eotaxin. This novel function of IL-21 may be associated with the attenuation of eosinophil infiltration into nasal mucosa that was revealed by histopathological observation. These results indicated that IL-21 nasal administration effectively ameliorated allergic rhinitis through pleiotropic activities, i.e., the prevention of IgE production by B cells and eotaxin production by fibroblasts.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Hiromura
authors.forename: Tsunao
authors.initials: T
authors.lastname: Kishida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakano
authors.forename: Takemitsu
authors.initials: T
authors.lastname: Hama
authors.forename: Jiro
authors.initials: J
authors.lastname: Imanishi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Hisa
authors.forename: Osam
authors.initials: O
authors.lastname: Mazda
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology; D004804:Eosinophils / Q000276:immunology / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000276:immunology* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology; D007378:Interleukins / Q000008:administration & dosage* / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000633:toxicity; D014066:Palatine Tonsil / Q000276:immunology* / Q000473:pathology; D051560:Proto-Oncogene Proteins c-bcl-6; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D000098546:Interleukin-21
chemical_list: C490010:Bcl6 protein, mouse; D016207:Cytokines; D004268:DNA-Binding Proteins; D007378:Interleukins; D051560:Proto-Oncogene Proteins c-bcl-6; D011994:Recombinant Proteins; D007073:Immunoglobulin E; D010047:Ovalbumin; D000098546:Interleukin-21