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Nat Immunol. 2018 Oct;19(10):1093-1099. doi: 10.1038/s41590-018-0201-4. Epub 2018 Sep 10.

Tissue signals imprint ILC2 identity with anticipatory function.

Author information

1
Department of Dermatology, University of California San Francisco, San Francisco, CA, USA.
2
Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
3
Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, USA.
4
Department of Epidemiology and Biostatistics, Institute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.
5
Lung Biology Center, University of California San Francisco, San Francisco, CA, USA.
6
Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA.
7
Department of Medicine, University of California San Francisco, San Francisco, CA, USA. Richard.Locksley@ucsf.edu.
8
Howard Hughes Medical Institute, University of California San Francisco, San Francisco, CA, USA. Richard.Locksley@ucsf.edu.

Abstract

Group 2 innate lymphoid cells (ILC2s) are distributed systemically and produce type 2 cytokines in response to a variety of stimuli, including the epithelial cytokines interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP). Transcriptional profiling of ILC2s from different tissues, however, grouped ILC2s according to their tissue of origin, even in the setting of combined IL-25-, IL-33-receptor-, and TSLP-receptor-deficiency. Single-cell profiling confirmed a tissue-organizing transcriptome and identified ILC2 subsets expressing distinct activating receptors, including the major subset of skin ILC2s, which were activated preferentially by IL-18. Tissue ILC2 subsets were unaltered in number and expression in germ-free mice, suggesting that endogenous, tissue-derived signals drive the maturation of ILC2 subsets by controlling expression of distinct patterns of activating receptors, thus anticipating tissue-specific perturbations occurring later in life.

Comment in

PMID:
30201992
PMCID:
PMC6202223
DOI:
10.1038/s41590-018-0201-4
[Indexed for MEDLINE]
Free PMC Article

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