Single-cell RNA-seq identifies a PD-1hi ILC progenitor and defines its development pathway - PubMed (original) (raw)

. 2016 Nov 3;539(7627):102-106.

doi: 10.1038/nature20105. Epub 2016 Sep 29.

Jason C H Tsang 1 2 3, Cui Wang 1 4, Simon Clare 1, Juexuan Wang 1, Xi Chen 1, Cordelia Brandt 1, Leanne Kane 1, Lia S Campos 1, Liming Lu 5, Gabrielle T Belz 6 7, Andrew N J McKenzie 8, Sarah A Teichmann 1 9, Gordon Dougan 1 10, Pentao Liu 1

Affiliations

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

Yong Yu et al. Nature. 2016.

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-1hi) marked a committed ILC progenitor that was essentially identical to an innate lymphoid cell progenitor. Our data defined PD-1hiIL-25Rhi 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-1hi 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.

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