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Nat Immunol. 2016 Jun;17(6):646-55. doi: 10.1038/ni.3447. Epub 2016 Apr 25.

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

Author information

1
Baylor Research Institute, Baylor Scott and White Health, Dallas, Texas, USA.
2
R&D Research, MedImmune, Gaithersburg, Maryland, USA.
3
Department of Respiratory, Inflammation and Autoimmunity, MedImmune, Gaithersburg, Maryland, USA.

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.

PMID:
27111142
DOI:
10.1038/ni.3447
[Indexed for MEDLINE]

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