title: Epicutaneous Allergic Sensitization by Cooperation between Allergen Protease Activity and Mechanical Skin Barrier Damage in Mice.
abstract: Allergen sources such as mites, insects, fungi, and pollen contain proteases. Airway exposure to proteases induces allergic airway inflammation and IgE/IgG1 responses via IL-33-dependent mechanisms in mice. We examined the epicutaneous sensitization of mice to a model protease allergen, papain; the effects of tape stripping, which induces epidermal barrier dysfunction; and the atopic march upon a subsequent airway challenge. Papain painting on ear skin and tape stripping cooperatively promoted dermatitis, the skin gene expression of proinflammatory cytokines and growth factors, up-regulation of serum total IgE, and papain-specific IgE/IgG1 induction. Epicutaneous sensitization induced T helper (Th) 2 cells and Th17 differentiation in draining lymph nodes. Ovalbumin and protease inhibitor-treated papain induced no or weak responses, whereas the co-administration of ovalbumin and papain promoted ovalbumin-specific IgE/IgG1 induction. Wild-type and IL-33-deficient mice showed similar responses in the epicutaneous sensitization phase. The subsequent airway papain challenge induced airway eosinophilia and maintained high papain-specific IgE levels in an IL-33-dependent manner. These results suggest that allergen source-derived protease activity and mechanical barrier damage such as that caused by scratching cooperatively promote epicutaneous sensitization and skin inflammation and that IL-33 is dispensable for epicutaneous sensitization but is crucial in the atopic march upon a subsequent airway low-dose encounter with protease allergens.
authors.affiliation: Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Dermatology and Allergology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Sakiko
authors.initials: S
authors.lastname: Shimura
authors.affiliation: Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan. Electronic address: t-takai@juntendo.ac.jp.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Takai
authors.affiliation: Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Dermatology and Allergology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Iida
authors.affiliation: Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Dermatology and Allergology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Maruyama
authors.affiliation: Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Dermatology and Allergology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Hirono
authors.initials: H
authors.lastname: Ochi
authors.affiliation: Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Kamijo
authors.affiliation: Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Dermatology and Allergology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Nishioka
authors.affiliation: Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Hara
authors.affiliation: Department of Ophthalmology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuda
authors.affiliation: Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Saito
authors.affiliation: Laboratory of Systems Biology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Sciences, The University of Tokyo, Tokyo, Japan; Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, Saitama, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakae
authors.affiliation: Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Dermatology and Allergology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Hideoki
authors.initials: H
authors.lastname: Ogawa
authors.affiliation: Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.affiliation: Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Dermatology and Allergology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Shigaku
authors.initials: S
authors.lastname: Ikeda
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D003872:Dermatitis / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006967:Hypersensitivity / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007249:Inflammation; D000067596:Interleukin-33 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin; D010206:Papain / Q000276:immunology; D011480:Protease Inhibitors / Q000737:chemistry; D060888:Real-Time Polymerase Chain Reaction; D012867:Skin / Q000187:drug effects / Q000276:immunology* / Q000293:injuries*; D013314:Stress, Mechanical; D058504:Th17 Cells / Q000166:cytology; D018418:Th2 Cells / Q000166:cytology; D014947:Wounds and Injuries / Q000378:metabolism
chemical_list: D000485:Allergens; D016207:Cytokines; C506535:Il33 protein, mouse; D007074:Immunoglobulin G; D000067596:Interleukin-33; D011480:Protease Inhibitors; D007073:Immunoglobulin E; D010047:Ovalbumin; D010206:Papain