File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

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

TitleSingle-cell RNA-seq identifies a PD-1<sup>hi</sup> ILC progenitor and defines its development pathway
Authors
Issue Date2016
Citation
Nature, 2016, v. 539, n. 7627, p. 102-106 How to Cite?
Abstract© 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. 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 inflammation. These results provide a perspective for exploring PD-1 and its ligand (PD-L1) in immunotherapy, and allow effective manipulation of the immune system for disease prevention and therapy.
Persistent Identifierhttp://hdl.handle.net/10722/249131
ISSN
2017 Impact Factor: 41.577
2015 SCImago Journal Rankings: 21.936
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorYu, Yong-
dc.contributor.authorTsang, Jason C.H.-
dc.contributor.authorWang, Cui-
dc.contributor.authorClare, Simon-
dc.contributor.authorWang, Juexuan-
dc.contributor.authorChen, Xi-
dc.contributor.authorBrandt, Cordelia-
dc.contributor.authorKane, Leanne-
dc.contributor.authorCampos, Lia S.-
dc.contributor.authorLu, Liming-
dc.contributor.authorBelz, Gabrielle T.-
dc.contributor.authorMcKenzie, Andrew N.J.-
dc.contributor.authorTeichmann, Sarah A.-
dc.contributor.authorDougan, Gordon-
dc.contributor.authorLiu, Pentao-
dc.date.accessioned2017-10-27T05:59:11Z-
dc.date.available2017-10-27T05:59:11Z-
dc.date.issued2016-
dc.identifier.citationNature, 2016, v. 539, n. 7627, p. 102-106-
dc.identifier.issn0028-0836-
dc.identifier.urihttp://hdl.handle.net/10722/249131-
dc.description.abstract© 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. 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 inflammation. These results provide a perspective for exploring PD-1 and its ligand (PD-L1) in immunotherapy, and allow effective manipulation of the immune system for disease prevention and therapy.-
dc.languageeng-
dc.relation.ispartofNature-
dc.titleSingle-cell RNA-seq identifies a PD-1<sup>hi</sup> ILC progenitor and defines its development pathway-
dc.typeArticle-
dc.description.natureLink_to_subscribed_fulltext-
dc.identifier.doi10.1038/nature20105-
dc.identifier.pmid27749818-
dc.identifier.scopuseid_2-s2.0-84994551721-
dc.identifier.volume539-
dc.identifier.issue7627-
dc.identifier.spage102-
dc.identifier.epage106-
dc.identifier.eissn1476-4687-
dc.identifier.isiWOS:000386670100038-
dc.identifier.f1000726853812-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats