title: Perinatal Activation of the Interleukin-33 Pathway Promotes Type 2 Immunity in the Developing Lung.
abstract: Allergic disease originates in early life and polymorphisms in interleukin-33 gene (IL33) and IL1RL1, coding for IL-33R and decoy receptor sST2, confer allergy risk. Early life T helper 2 (Th2) cell skewing and allergy susceptibility are often seen as remnants of feto-maternal symbiosis. Here we report that shortly after birth, innate lymphoid type 2 cells (ILC2s), eosinophils, basophils, and mast cells spontaneously accumulated in developing lungs in an IL-33-dependent manner. During the phase of postnatal lung alveolarization, house dust mite exposure further increased IL-33, which boosted cytokine production in ILC2s and activated CD11b+dendritic cells (DCs). IL-33 suppressed IL-12p35 and induced OX40L in neonatal DCs, thus promoting Th2 cell skewing. Decoy sST2 had a strong preventive effect on asthma in the neonatal period, less so in adulthood. Thus, enhanced neonatal Th2 cell skewing to inhaled allergens results from postnatal hyperactivity of the IL-33 axis during a period of maximal lung remodeling.
authors.affiliation: Department of Pulmonary Medicine, Erasmus University Medical Center Rotterdam, Rotterdam 3015 GJ, the Netherlands; Laboratory of Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, Ghent 9050, Belgium; Department of Pulmonary Medicine, Ghent University, Ghent 9000, Belgium; Department of Pediatric Pulmonology, Sophia's Children's Hospital, Erasmus University Medical Center Rotterdam, Rotterdam 3015 GJ, the Netherlands. Electronic address: i.dekleer@erasmusmc.nl.
authors.forename: Ismé M
authors.initials: IM
authors.lastname: de Kleer
authors.affiliation: Laboratory of Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, Ghent 9050, Belgium; Department of Pulmonary Medicine, Ghent University, Ghent 9000, Belgium.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Kool
authors.affiliation: Department of Pulmonary Medicine, Erasmus University Medical Center Rotterdam, Rotterdam 3015 GJ, the Netherlands.
authors.forename: Marjolein J W
authors.initials: MJ
authors.lastname: de Bruijn
authors.affiliation: Laboratory of Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, Ghent 9050, Belgium; Department of Pulmonary Medicine, Ghent University, Ghent 9000, Belgium.
authors.forename: Monique
authors.initials: M
authors.lastname: Willart
authors.affiliation: Laboratory of Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, Ghent 9050, Belgium; Department of Pulmonary Medicine, Ghent University, Ghent 9000, Belgium.
authors.forename: Justine
authors.initials: J
authors.lastname: van Moorleghem
authors.affiliation: Laboratory of Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, Ghent 9050, Belgium; Department of Pulmonary Medicine, Ghent University, Ghent 9000, Belgium.
authors.forename: Martijn J
authors.initials: MJ
authors.lastname: Schuijs
authors.affiliation: Laboratory of Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, Ghent 9050, Belgium; Department of Pulmonary Medicine, Ghent University, Ghent 9000, Belgium; Laboratory of Cellular Immunology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht 3584 EA, the Netherlands.
authors.forename: Maud
authors.initials: M
authors.lastname: Plantinga
authors.affiliation: Unit of Molecular Signal Transduction in Inflammation, Department for Molecular Biomedical Research, VIB, Ghent 9050, Belgium.
authors.forename: Rudi
authors.initials: R
authors.lastname: Beyaert
authors.affiliation: School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Emily
authors.initials: E
authors.lastname: Hams
authors.affiliation: School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Padraic G
authors.initials: PG
authors.lastname: Fallon
authors.affiliation: Laboratory of Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, Ghent 9050, Belgium; Department of Pulmonary Medicine, Ghent University, Ghent 9000, Belgium.
authors.forename: Hamida
authors.initials: H
authors.lastname: Hammad
authors.affiliation: Department of Pulmonary Medicine, Erasmus University Medical Center Rotterdam, Rotterdam 3015 GJ, the Netherlands.
authors.forename: Rudi W
authors.initials: RW
authors.lastname: Hendriks
authors.affiliation: Department of Pulmonary Medicine, Erasmus University Medical Center Rotterdam, Rotterdam 3015 GJ, the Netherlands; Laboratory of Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, Ghent 9050, Belgium; Department of Pulmonary Medicine, Ghent University, Ghent 9000, Belgium. Electronic address: bart.lambrecht@ugent.be.
authors.forename: Bart N
authors.initials: BN
authors.lastname: Lambrecht
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001249:Asthma / Q000276:immunology*; D004195:Disease Models, Animal; D006967:Hypersensitivity / Q000276:immunology; D000067596:Interleukin-33 / Q000276:immunology*; D008168:Lung / Q000254:growth & development* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D039981:Pyroglyphidae / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
chemical_list: C506535:Il33 protein, mouse; D000067596:Interleukin-33
keywords: IL-33; IL1RL1; ILC2; allergic asthma; alveolarization; dendritic cells; early life; eosinophils; house dust mite; lung development