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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 2

ILC2s labeled with BrdU in the neonatal period respond more intensely than BrdU– ILC2s to IL-33 treatment later in life.

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ILC2s labeled with BrdU in the neonatal period respond more intensely th...
(A) BrdU was administered i.n. at postnatal day (d) 6–9. Lung ILC2s were analyzed at indicated ages for BrdU (n > 4). Shading indicates isotype control; white indicates anti-BrdU. (B) Adult mice were given BrdU in their drinking water for 6 weeks, as indicated by the scheme, and analyzed for ILC2 incorporation of BrdU. Numbers in the plot represent mean percentage ± SEM (n = 9, 2 independent experiments). (C) Mice received BrdU and IL-33 i.n. administrations as shown. (D) Lung ILC2s in PBS-injected and IL-33–injected mice were stained by anti-BrdU (white) or isotype control (shaded). Numbers in plots represent mean percentage ± SEM. The histogram on the right shows intracellular IL-13 in BrdU+ (red line) and BrdU– (black line) ILC2s from IL-33–injected mice with isotype control (shaded). Numbers in the plot show mean fluorescence intensity ± SEM. (E) Scatter plot shows the percentages of IL-13+ cells among BrdU+ (black) and BrdU– (white) ILC2s (n = 8, 2 independent experiments). *P < 0.05 (1-tailed unpaired Student’s t test).

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