2016-12-20
Perinatal Activation of the Interleukin-33 Pathway Promotes Type 2 Immunity in the Developing Lung
Publication
Publication
Immunity , Volume 45 - Issue 6 p. 1285- 1298
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.
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doi.org/10.1016/j.immuni.2016.10.031, hdl.handle.net/1765/95079 | |
Immunity | |
Organisation | Department of Pulmonology |
de Kleer, I., Kool, M., de Bruijn, M., Willart, M., van Moorleghem, J. (Justine), Schuijs, M., … Lambrecht, B. (2016). Perinatal Activation of the Interleukin-33 Pathway Promotes Type 2 Immunity in the Developing Lung. Immunity, 45(6), 1285–1298. doi:10.1016/j.immuni.2016.10.031 |