title: IL-33 citrine reporter mice reveal the temporal and spatial expression of IL-33 during allergic lung inflammation.
abstract: Interleukin-33 (IL-33) is an IL-1 family cytokine that signals via its receptor T1/ST2, and is a key regulator of inflammation, notably the type-2 response implicated in allergic asthma. Critical to our understanding of the role of IL-33 is the identification of the cellular sources of IL-33. Although progress has been made in this area, the development of a robust live cell reporter of expression would allow the localisation of IL-33 during ongoing immune responses. We have generated a fluorescent reporter mouse line, Il33(Cit/+), to define the expression profile of IL-33 in vivo and demonstrate its temporal and spatial expression during experimental allergic asthma responses. We found that type-2 pneumocytes constitute the major source of IL-33 upon allergic lung inflammation following exposure to OVA, fungal extract or ragweed pollen. Using Il33(Cit/Cit) mice (IL-33-deficient), we establish a role for IL-33 early in the initiation of type-2 responses and the induction of nuocytes (ILC2). We also demonstrate a potential mechanism of action by which IL-33 rapidly initiates type-2 immune responses. Il33(Cit/+) mice have enabled new insights into the initiation of type-2 responses and will provide an important tool for further dissection of this important inflammatory pathway in vivo.
authors.affiliation: MRC Laboratory of Molecular Biology, Hills Road, Cambridge, UK.
authors.forename: Clare S
authors.initials: CS
authors.lastname: Hardman
authors.forename: Veera
authors.initials: V
authors.lastname: Panova
authors.forename: Andrew N J
authors.initials: AN
authors.lastname: McKenzie
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005658:Fungi / Q000276:immunology; D000067596:Interleukin-33; D007378:Interleukins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011014:Pneumonia / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011058:Pollen / Q000276:immunology; D011401:Promoter Regions, Genetic
chemical_list: D000485:Allergens; C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007378:Interleukins