title: Critical role of caspase-8-mediated IL-1 signaling in promoting Th2 responses during asthma pathogenesis.
abstract: Allergic asthma is a chronic inflammatory disorder of the airways that affects >300 million people worldwide. The pro-inflammatory cytokines interleukin (IL)-1α and IL-1β have essential roles in the pathogenesis of asthma. However, the mechanisms underlying the production of IL-1 cytokines in allergic asthma remain unclear. In this study, we used a mouse model of ovalbumin-induced asthma to identify a crucial role for caspase-8 in the development of allergic airway inflammation. We further demonstrated that hematopoietic cells have dominant roles in caspase-8-mediated allergic airway inflammation. Caspase-8 was required for the production of IL-1 cytokines to promote Th2 immune response, which promotes the development of pulmonary eosinophilia and inflammation. Thus, our study identifies caspase-8 as a master regulator of IL-1 cytokines that contribute to the pathogenesis of asthma and implicates caspase-8 inhibition as a potential therapeutic strategy for asthmatic patients.
authors.affiliation: Department of Immunology, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: X
authors.initials: X
authors.lastname: Qi
authors.affiliation: Department of Immunology, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: P
authors.initials: P
authors.lastname: Gurung
authors.affiliation: Department of Immunology, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: R K S
authors.initials: RK
authors.lastname: Malireddi
authors.affiliation: Department of Immunology, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: P W F
authors.initials: PW
authors.lastname: Karmaus
authors.affiliation: Department of Immunology, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: D
authors.initials: D
authors.lastname: Sharma
authors.affiliation: Department of Veterinary Pathology Core, Animal Resources Center and the Veterinary Pathology Core, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: P
authors.initials: P
authors.lastname: Vogel
authors.affiliation: Department of Immunology, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: H
authors.initials: H
authors.lastname: Chi
authors.affiliation: Department of Immunology, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Green
authors.affiliation: Department of Immunology, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: T-D
authors.initials: TD
authors.lastname: Kanneganti
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology*; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007375:Interleukin-1 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D015398:Signal Transduction; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000485:Allergens; D007375:Interleukin-1; D010047:Ovalbumin; D053181:Caspase 8