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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 4

Comparison of IL-33–deficient and WT adult ILC2s.

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Comparison of IL-33–deficient and WT adult ILC2s.
(A) Heatmap shows the ...
(A) Heatmap shows the relative expression levels of genes that are differentially expressed in lung ILC2s from adult IL-33–deficient (KO) (n = 2) and WT mice (n = 3). Each replicate represents sorted ILC2s from 8 pooled mice *Genes in red indicate those that are differentially expressed more than 2-fold between KO and WT ILC2s. (B) Flow cytometry plots show expression of CD24, ICOS, and intracellular TNF-α on KO (black) and WT (red) adult mouse lung ILC2s (n = 6). Numbers in the plots indicate the mean percentage ± SEM. (C) Histogram shows ST2 expression on KO and WT ILC2s. Shading indicates isotype control. *P < 0.05; **P < 0.01. (1-tailed unpaired Student’s t test for B and C).

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