IL-1 is a critical regulator of group 2 innate lymphoid cell function and plasticity

Y Ohne, JS Silver, LA Thompson-Snipes… - Nature …, 2016 - nature.com
Y Ohne, JS Silver, LA Thompson-Snipes, MA Collet, JP Blanck, BL Cantarel
Nature immunology, 2016nature.com
Group 2 innate lymphoid cells (ILC2 cells) are important for type 2 immune responses and
are activated by the epithelial cytokines interleukin 33 (IL-33), IL-25 and thymic stromal
lymphopoietin (TSLP). Here we demonstrated that IL-1β was a critical activator of ILC2 cells,
inducing proliferation and cytokine production and regulating the expression of epithelial
cytokine receptors. IL-1β also governed ILC2 plasticity by inducing low expression of the
transcription factor T-bet and the cytokine receptor chain IL-12Rβ2, which enabled the …
Abstract
Group 2 innate lymphoid cells (ILC2 cells) are important for type 2 immune responses and are activated by the epithelial cytokines interleukin 33 (IL-33), IL-25 and thymic stromal lymphopoietin (TSLP). Here we demonstrated that IL-1β was a critical activator of ILC2 cells, inducing proliferation and cytokine production and regulating the expression of epithelial cytokine receptors. IL-1β also governed ILC2 plasticity by inducing low expression of the transcription factor T-bet and the cytokine receptor chain IL-12Rβ2, which enabled the conversion of these cells into an ILC1 phenotype in response to IL-12. This transition was marked by an atypical chromatin landscape characterized by the simultaneous transcriptional accessibility of the locus encoding interferon-γ (IFN-γ) and the loci encoding IL-5 and IL-13. Finally, IL-1β potentiated ILC2 activation and plasticity in vivo, and IL-12 acted as the switch that determined an ILC2-versus-ILC1 response. Thus, we have identified a previously unknown role for IL-1β in facilitating ILC2 maturation and plasticity.
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