title: Thymic stromal lymphopoietin (TSLP)-mediated dermal inflammation aggravates experimental asthma.
abstract: Individuals with one atopic disease are far more likely to develop a second. Approximately half of all atopic dermatitis (AD) patients subsequently develop asthma, particularly those with severe AD. This association, suggesting a role for AD as an entry point for subsequent allergic disease, is a phenomenon known as the "atopic march." Although the underlying cause of the atopic march remains unknown, recent evidence suggests a role for the cytokine thymic stromal lymphopoietin (TSLP). We have established a mouse model to determine whether TSLP plays a role in this phenomenon, and in this study show that mice exposed to the antigen ovalbumin (OVA) in the skin in the presence of TSLP develop severe airway inflammation when later challenged with the same antigen in the lung. Interestingly, neither TSLP production in the lung nor circulating TSLP is required to aggravate the asthma that was induced upon subsequent antigen challenge. However, CD4 T cells are required in the challenge phase of the response, as was challenge with the sensitizing antigen, demonstrating that the response was antigen specific. This study, which provides a clean mouse model to study human atopic march, indicates that skin-derived TSLP may represent an important factor that triggers progression from AD to asthma.
authors.affiliation: Immunology Program, Benaroya Research Institute, Seattle, Washington, USA.
authors.forename: H
authors.initials: H
authors.lastname: Han
authors.forename: W
authors.initials: W
authors.lastname: Xu
authors.forename: M B
authors.initials: MB
authors.lastname: Headley
authors.forename: H K
authors.initials: HK
authors.lastname: Jessup
authors.forename: K S
authors.initials: KS
authors.lastname: Lee
authors.forename: M
authors.initials: M
authors.lastname: Omori
authors.forename: M R
authors.initials: MR
authors.lastname: Comeau
authors.forename: A
authors.initials: A
authors.lastname: Marshak-Rothstein
authors.forename: S F
authors.initials: SF
authors.lastname: Ziegler
mesh_terms: D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000150:complications / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000008:administration & dosage / Q000276:immunology*; D003876:Dermatitis, Atopic / Q000150:complications / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D007114:Immunization; D007271:Injections, Intradermal; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011014:Pneumonia / Q000276:immunology*; D012867:Skin / Q000276:immunology; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D000485:Allergens; D016207:Cytokines; D010047:Ovalbumin; D000094632:Thymic Stromal Lymphopoietin