Cited by 309IL-33, ST2, and ILC PathwaysT-cell and B-cell ImmunologyAsthma and respiratory diseases

Single-cell RNA-seq identifies a PD-1hi ILC progenitor and defines its development pathway

Yu, Yong, Tsang, Jason C. H., Wang, Cui, Clare, Simon, Wang, Juexuan, Chen, Xi, Brandt, Cordelia, Kane, Leanne +7 more·2016·Nature

Abstract

Innate lymphoid cells (ILCs) functionally resemble T lymphocytes in cytotoxicity and cytokine production but lack antigen-specific receptors, and they are important regulators of immune responses and tissue homeostasis. ILCs are generated from common lymphoid progenitors, which are subsequently committed to innate lymphoid lineages in the α-lymphoid progenitor, early innate lymphoid progenitor, common helper innate lymphoid progenitor and innate lymphoid cell progenitor compartments. ILCs consist of conventional natural killer cells and helper-like cells (ILC1, ILC2 and ILC3). Despite recent advances, the cellular heterogeneity, developmental trajectory and signalling dependence of ILC progenitors are not fully understood. Here, using single-cell RNA-sequencing (scRNA-seq) of mouse bone marrow progenitors, we reveal ILC precursor subsets, delineate distinct ILC development stages and pathways, and report that high expression of programmed death 1 (PD-1 hi ) marked a committed ILC progenitor that was essentially identical to an innate lymphoid cell progenitor. Our data defined PD-1 hi IL-25R hi as an early checkpoint in ILC2 development, which was abolished by deficiency in the zinc-finger protein Bcl11b but restored by IL-25R overexpression. Similar to T lymphocytes, PD-1 was upregulated on activated ILCs. Administration of a PD-1 antibody depleted PD-1 hi ILCs and reduced cytokine levels in an influenza infection model in mice, and blocked papain-induced acute lung inflammat…

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Crossref · 10.1038/nature20105

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Authors
Yu, Y., Tsang, J. C. H., Wang, C., Clare, S., Wang, J., Chen, X., Brandt, C., Kane, L., Campos, L. S., Lu, L., Belz, G. T., McKenzie, A. N. J., Teichmann, S. A., Dougan, G., & Liu, P.
Affiliations
  • Wellcome Sanger Institute (GB)
  • Chinese University of Hong Kong (HK)
  • Shanghai Jiao Tong University (CN)
  • The University of Melbourne (AU)
  • MRC Laboratory of Molecular Biology (GB)
  • European Bioinformatics Institute (GB)
Corresponding author
Liu, Pentao
Venue
Nature
Published
2016-09-29
Volume
539
Issue
7627
Pages
102-106
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2525469791
Cited by
306
References
41
Citations by year
2026: 12 · 2025: 23 · 2024: 23 · 2023: 27 · 2022: 35 · 2021: 36 · 2020: 46 · 2019: 39 · 2018: 32 · 2017: 31 · 2016: 1 · 2014: 1
FWCI
20.82
Type
journal article
Language
en
Open access
closed
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
Funders
Wellcome Trust (100963/Z/13/Z, 098051)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
Keywords
innate lymphoid cells, PD-1, BCL11B, IL-25 receptor, influenza, acute lung inflammation, bone marrow progenitor cells, cytokine production, tissue homeostasis
MeSH terms
Animals, Antibodies, Base Sequence, Cell Differentiation, Cell Separation, Disease Models, Animal, Humans, Immunity, Innate, Immunotherapy, Influenza, Human, Killer Cells, Natural, Lymphocyte Activation, Lymphocytes, Mice, Inbred C57BL, Pneumonia, Repressor Proteins, T-Lymphocytes, Cytokines, Receptors, Interleukin, Cell Lineage, Tumor Suppressor Proteins, Mice, Lymphoid Progenitor Cells, Single-Cell Analysis, Programmed Cell Death 1 Receptor

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