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Lung group 2 innate lymphoid cells are trained by endogenous IL-33 in the neonatal period
Catherine A. Steer, … , Hanjoo Shim, Fumio Takei
Catherine A. Steer, … , Hanjoo Shim, Fumio Takei
Published June 23, 2020
Citation Information: JCI Insight. 2020;5(14):e135961. https://doi.org/10.1172/jci.insight.135961.
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Research Article Immunology

Lung group 2 innate lymphoid cells are trained by endogenous IL-33 in the neonatal period

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Abstract

Group 2 innate lymphoid cells (ILC2s) in mouse lungs are activated by the epithelium-derived alarmin IL-33. Activated ILC2s proliferate and produce IL-5 and IL-13 that drive allergic responses. In neonatal lungs, the occurrence of spontaneous activation of lung ILC2s is dependent on endogenous IL-33. Here, we report that neonatal lung ILC2 activation by endogenous IL-33 has significant effects on ILC2 functions in adulthood. Most neonatal lung ILC2s incorporated 5-bromo-2′-deoxyuridine (BrdU) and persisted into adulthood. BrdU+ ILC2s in adult lungs responded more intensely to IL-33 treatment compared with BrdU– ILC2s. In IL-33–deficient (KO) mice, lung ILC2s develop normally, but they are not activated in the neonatal period. Lung ILC2s in KO mice responded less intensely to IL-33 in adulthood compared with WT ILC2s. While there was no difference in the number of lung ILC2s, there were fewer IL-13+ ILC2s in KO mice compared with those in WT mice. The impaired responsiveness of ILC2s in KO mice was reversed by i.n. administrations of IL-33 in the neonatal period. These results suggest that activation of lung ILC2s by endogenous IL-33 in the neonatal period may “train” ILC2s seeding the lung after birth to become long-lasting resident cells that respond more efficiently to challenges later in life.

Authors

Catherine A. Steer, Laura Mathä, Hanjoo Shim, Fumio Takei

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Figure 3

ILC2s from IL-33–deficient mice respond more weakly than WT mice to IL-33 treatment.

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ILC2s from IL-33–deficient mice respond more weakly than WT mice to IL-3...
(A) Adult WT (red) and KO (black) mice at 8 weeks of age received 2 daily i.n. IL-33 administrations and were analyzed 3 days later (n = 9, 3 independent experiments). (B) Total number of lung ILC2s in naive and IL-33–treated WT and KO mice. (C) Plots show intracellular IL-5 and IL-13 expression in WT and KO ILC2s. Numbers in plots represent mean percentage ± SEM. (D) Histograms of intracellular IL-13 and IL-5 staining in WT and KO ILC2s. Numbers in plots represent mean percentage ± SEM. Shading indicates isotype control. (E) Numbers of IL-13+ and IL-5+ ILC2s. (F) Eosinophil numbers in the lung. (G) The amount of IL-13 and IL-5 in the bronchoalveolar lavage. (H) Mucus production by PAS staining of lung tissue sections and PAS+ area (mm2 per mm of basement membrane) (n = 4). Scale bar: 0.05 mm. *P < 0.05; **P < 0.01; ****P < 0.0001 (1-tailed unpaired Student’s t test).

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