title: IL-33-mediated innate response and adaptive immune cells contribute to maximum responses of protease allergen-induced allergic airway inflammation.
abstract: How the innate and adaptive immune systems cooperate in the natural history of allergic diseases has been largely unknown. Plant-derived allergen, papain, and mite allergens, Der f 1 and Der p 1, belong to the same family of cysteine proteases. We examined the role of protease allergens in the induction of Ab production and airway inflammation after repeated intranasal administration without adjuvants and that in basophil/mast cell stimulation in vitro. Papain induced papain-specific IgE/IgG1 and lung eosinophilia. Der f 1 induced Der f 1-specific IgG1 and eosinophilia. Although papain-, Der f 1-, and Der p 1-stimulated basophils expressed allergy-inducing cytokines, including IL-4 in vitro, basophil-depleting Ab and mast cell deficiency did not suppress the papain-induced in vivo responses. Protease inhibitor-treated allergens and a catalytic site mutant did not induce the responses. These results indicate that protease activity is essential to Ab production and eosinophilia in vivo and basophil activation in vitro. IL-33-deficient mice lacked eosinophilia and had reduced papain-specific IgE/IgG1. Coadministration of OVA with papain induced OVA-specific IgE/IgG1, which was reduced in IL-33-deficient mice. We demonstrated IL-33 release, subsequent IL-33-dependent IL-5/IL-13 release, and activation of T1/ST2-expressing lineage(-)CD25(+)CD44(+) innate lymphoid cells in the lung after papain inhalation, suggesting the contribution of the IL-33-type 2 innate lymphoid cell-IL-5/IL-13 axis to the papain-induced airway eosinophilia. Rag2-deficient mice, which lack adaptive immune cells, showed significant, but less severe, eosinophilia. Collectively, these results suggest cooperation of adaptive immune cells and IL-33-responsive innate cells in protease-dependent allergic airway inflammation.
authors.affiliation: Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Kamijo
authors.forename: Haruna
authors.initials: H
authors.lastname: Takeda
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tokura
authors.forename: Mayu
authors.initials: M
authors.lastname: Suzuki
authors.forename: Kyoko
authors.initials: K
authors.lastname: Inui
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Hara
authors.forename: Hironori
authors.initials: H
authors.lastname: Matsuda
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuda
authors.forename: Keisuke
authors.initials: K
authors.lastname: Oboki
authors.forename: Tatsukuni
authors.initials: T
authors.lastname: Ohno
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Saito
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakae
authors.forename: Katsuko
authors.initials: K
authors.lastname: Sudo
authors.forename: Hajime
authors.initials: H
authors.lastname: Suto
authors.forename: Saori
authors.initials: S
authors.lastname: Ichikawa
authors.forename: Hideoki
authors.initials: H
authors.lastname: Ogawa
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.forename: Toshiro
authors.initials: T
authors.lastname: Takai
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000485:Allergens / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D039741:Antigens, Dermatophagoides / Q000276:immunology; D060829:Arthropod Proteins / Q000276:immunology; D001491:Basophils / Q000276:immunology; D003546:Cysteine Endopeptidases / Q000276:immunology; D057056:Cysteine Proteases / Q000276:immunology*; D005260:Female; D006967:Hypersensitivity / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D018793:Interleukin-13 / Q000276:immunology; D000067596:Interleukin-33; D015848:Interleukin-5 / Q000276:immunology; D007378:Interleukins / Q000276:immunology*; D008168:Lung / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010206:Papain / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000276:immunology
chemical_list: D000485:Allergens; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; C506535:Il33 protein, mouse; D007074:Immunoglobulin G; D018793:Interleukin-13; D000067596:Interleukin-33; D015848:Interleukin-5; D007378:Interleukins; D007073:Immunoglobulin E; D057056:Cysteine Proteases; D003546:Cysteine Endopeptidases; C451159:Dermatophagoides farinae antigen f 1; C451162:Dermatophagoides pteronyssinus antigen p 1; D010206:Papain