title: Endogenous IL-33 enhances Th2 cytokine production and T-cell responses during allergic airway inflammation.
abstract: IL-33 is an IL-1-related cytokine which has been implicated in T(h)2-associated biology and allergic diseases in humans and mice. IL-33 stimulates T(h)2 cells, mast cells, eosinophils, basophils, iNKT cells and circulating CD34(+) stem cells to proliferate and produce pro-allergic cytokines such as IL-5 and IL-13. IL-33 mediates its cytokine effects through a receptor consisting of ST2 and IL-1RAcP. Whereas IL-1RAcP is ubiquitously expressed, ST2 expression is cell-type restricted and determines responsiveness to IL-33. Studies employing ST2-deficient mice have reported variable results on the role of this receptor, and consequently IL-33, with regards to allergic lung inflammation. In this study, we demonstrate that IL-33 is important for allergic lung inflammation. Intra-nasal administration of IL-33 triggered an immediate allergic response in the airways, and more importantly, we show that endogenous IL-33 contributes to airway inflammation and peripheral antigen-specific responses in ovalbumin-induced acute allergic lung inflammation using IL-33-deficient mice. Our results suggest that IL-33 is sufficient and required for severe allergic inflammation in the lung and support the concept of IL-33 as a therapeutic target in allergic lung inflammation.
authors.affiliation: Department of Immunology, Merck Research Laboratories (formerly Schering-Plough Biopharma), Palo Alto, CA 94304, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Louten
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Rankin
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Erin E
authors.initials: EE
authors.lastname: Murphy
authors.forename: Maribel
authors.initials: M
authors.lastname: Beaumont
authors.forename: Christina
authors.initials: C
authors.lastname: Moon
authors.forename: Patricia
authors.initials: P
authors.lastname: Bourne
authors.forename: Terrill K
authors.initials: TK
authors.lastname: McClanahan
authors.forename: Stefan
authors.initials: S
authors.lastname: Pflanz
authors.forename: Rene
authors.initials: R
authors.lastname: de Waal Malefyt
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D000067596:Interleukin-33; D007378:Interleukins / Q000172:deficiency / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism*
chemical_list: D016207:Cytokines; C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007378:Interleukins