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

2016; Cell Press; Volume: 45; Issue: 6 Linguagem: Inglês

10.1016/j.immuni.2016.10.031

1097-4180

Ismé M. de Kleer, Mirjam Kool, Marjolein J. W. de Bruijn, Monique Willart, Justine Van Moorleghem, Martijn J. Schuijs, Maud Plantinga, Rudi Beyaert, Emily Hams, Padraic G. Fallon, Hamida Hammad, Rudi W. Hendriks, Bart N. Lambrecht,

Eosinophilic Esophagitis

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.