title: Murine allergic rhinitis and nasal Th2 activation are mediated via TSLP- and IL-33-signaling pathways.
abstract: Thymic stromal lymphopoietin (TSLP) and IL-33 are epithelium-derived proallergic cytokines that contribute to allergic diseases. Although the involvement of TSLP in allergic rhinitis (AR) is suggested, the exact role of TSLP in AR is poorly understood. Furthermore, the relative contribution of TSLP and IL-33 in nasal allergic responses has not been described. In this study, we examined the roles of TSLP and IL-33 in AR by analyzing acute and chronic AR models. Acute AR mice were intraperitoneally immunized with ragweed, then intranasally challenged with ragweed pollen for four consecutive days. Chronic AR mice were nasally administrated ragweed pollen on consecutive days for 3 weeks. In both models, TSLP receptor (TSLPR)-deficient mice showed defective sneezing responses and reduced serum ragweed-specific IgE levels compared with wild-type (WT) mice. Analyses of bone-marrow chimeric mice demonstrated that hematopoietic cells were responsible for defective sneezing in TSLPR-deficient mice. In addition, FcεRI(+)-cell-specific TSLPR-deficient mice showed partial but significant reduction in sneezing responses. Of note, Th2 activation and nasal eosinophilia were comparable between WT and TSLPR-deficient mice. ST2- and IL-33-deficient mice showed defective Th2 activation and nasal eosinophilia to acute, but not chronic, ragweed exposure. TSLPR and ST2 double-deficient mice showed defective Th2 activation and nasal eosinophilia even after chronic ragweed exposure. These results demonstrate that TSLPR signaling is critical for the early phase response of AR by controlling the IgE-mast-cell/basophil pathway. The IL-33/ST2 pathway is central to nasal Th2 activation during acute allergen exposure, but both TSLPR and ST2 contribute to Th2 responses in chronically allergen-exposed mice.
authors.affiliation: Laboratory of Allergic Diseases, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Akasaki
authors.affiliation: Laboratory of Allergic Diseases, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Matsushita
authors.affiliation: Laboratory of Allergic Diseases, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan Department of Otorhinolaryngology-Head and Neck Surgery, Faculty of Medical Science, University of Fukui, Fukui 910-1193, Japan.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Laboratory of Allergic Diseases, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Fukuoka
authors.affiliation: Laboratory of Allergic Diseases, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan Department of Otorhinolaryngology, Shiga University of Medical Science, Otsu, Shiga 520-2121, Japan.
authors.forename: Naruhito
authors.initials: N
authors.lastname: Iwasaki
authors.affiliation: Department of Immunology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Masakiyo
authors.initials: M
authors.lastname: Nakahira
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Faculty of Medical Science, University of Fukui, Fukui 910-1193, Japan.
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Fujieda
authors.affiliation: Department of Immunology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Koubun
authors.initials: K
authors.lastname: Yasuda
authors.affiliation: Laboratory of Allergic Diseases, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan Department of Immunology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan tomo@hyo-med.ac.jp.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yoshimoto
mesh_terms: D000208:Acute Disease; D000485:Allergens / Q000276:immunology; D031164:Ambrosia; D000818:Animals; D052179:Antigens, Plant / Q000276:immunology; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000235:genetics / Q000378:metabolism*; D000067596:Interleukin-33 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009297:Nasal Mucosa / Q000276:immunology*; D011058:Pollen / Q000276:immunology; D018121:Receptors, Cytokine / Q000235:genetics; D017455:Receptors, IgE / Q000235:genetics; D065631:Rhinitis, Allergic / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics; D018418:Th2 Cells / Q000502:physiology*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D000485:Allergens; D052179:Antigens, Plant; D016207:Cytokines; C579617:FcepsilonRIalpha protein, mouse; C486189:Il1rl1 protein, mouse; D007136:Immunoglobulins; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D018121:Receptors, Cytokine; D017455:Receptors, IgE; C410591:Tslpr protein, mouse; D000094632:Thymic Stromal Lymphopoietin
keywords: immunoglobulin E; interleukin-33; mast cells; nose; thymic stromal lymphopoietin