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Immunity. 2016 Dec 20;45(6):1285-1298. doi: 10.1016/j.immuni.2016.10.031. Epub 2016 Dec 6.

Perinatal Activation of the Interleukin-33 Pathway Promotes Type 2 Immunity in the Developing Lung.

Author information

1
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.
2
Laboratory of Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, Ghent 9050, Belgium; Department of Pulmonary Medicine, Ghent University, Ghent 9000, Belgium.
3
Department of Pulmonary Medicine, Erasmus University Medical Center Rotterdam, Rotterdam 3015 GJ, the Netherlands.
4
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.
5
Unit of Molecular Signal Transduction in Inflammation, Department for Molecular Biomedical Research, VIB, Ghent 9050, Belgium.
6
School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
7
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.

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.

KEYWORDS:

IL-33; IL1RL1; ILC2; allergic asthma; alveolarization; dendritic cells; early life; eosinophils; house dust mite; lung development

PMID:
27939673
DOI:
10.1016/j.immuni.2016.10.031
[Indexed for MEDLINE]
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