A single-cell transcriptional reference for the functional and developmental diversity of neonatal innate lymphoid cells

Cell Reports, vol. 45, pp. 117000

Abstract

Circulating innate lymphoid cells (cILCs) comprise a complex mixture of subsets with effector functions and progenitor potential toward mature ILCs and natural killer (NK) cells. Here, we dissected cord blood (CB) cILC complexity using single-cell RNA sequencing (RNA-seq) combined with developmental and functional analyses. cILC1s comprise six different subsets, with four showing different maturation degrees and two resembling NK cell progenitors. Despite previously described transcriptional similarity to T cells, the developmental potential of cILC1s was restricted to NK cells using an artificial thymic organoid (ATO) model. cILC2s could be divided into four main subsets: CD161 + , CD117 + , activated cILC2s, and cytotoxic cILC2s. Finally, a CD161 + CD28 + CD117 low ILC3 subset was identified that secreted IFNγ upon co-stimulation with a CD28 superagonist, suggesting an alternative activation stimulus for cILC3s. Altogether, this in-depth analysis provides a detailed picture of cILC diversity in immunologically naive CB and constitutes a versatile resource for further exploration of their translational potential.

Authors 11

1. Sabrina Bianca Bennstein corresponding Aachen Institute of Immunology Faculty of Medicine

   Heinrich Heine University Düsseldorf · RWTH Aachen University

   Affiliation as printed

   Institute for Transplantation Diagnostics and Cell Therapeutics, Medical Faculty, Heinrich-Heine University Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany; Institute of Immunology, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany. Electronic address: sabrina.bennstein1@rwth-aachen.de

2. Julian Reiß

   Heinrich Heine University Düsseldorf

   Affiliation as printed

   Institute for Transplantation Diagnostics and Cell Therapeutics, Medical Faculty, Heinrich-Heine University Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany

3. Katharina Raba

   Heinrich Heine University Düsseldorf

   Affiliation as printed

   Institute for Transplantation Diagnostics and Cell Therapeutics, Medical Faculty, Heinrich-Heine University Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany

4. Thi Xuan Uyen Pham

   Helios Klinikum Krefeld · Heinrich Heine University Düsseldorf

   Affiliation as printed

   Institute for Transplantation Diagnostics and Cell Therapeutics, Medical Faculty, Heinrich-Heine University Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany; Department of Pediatrics, Helios Klinikum Krefeld, Krefeld, Germany

5. Stefan Paulusch

   University of Bonn · German Center for Neurodegenerative Diseases

   Affiliation as printed

   PRECISE Platform for Genomics and Epigenomics at German Center for Neurodegenerative Diseases (DZNE) and University of Bonn and West German Genome Center, Bonn, Germany

6. Elena De Domenico

   University of Bonn · German Center for Neurodegenerative Diseases

   Affiliation as printed

   PRECISE Platform for Genomics and Epigenomics at German Center for Neurodegenerative Diseases (DZNE) and University of Bonn and West German Genome Center, Bonn, Germany

7. Tim Niehues

   Helios Klinikum Krefeld

   Affiliation as printed

   Department of Pediatrics, Helios Klinikum Krefeld, Krefeld, Germany

8. Johannes Fischer

   Heinrich Heine University Düsseldorf

   Affiliation as printed

   Institute for Transplantation Diagnostics and Cell Therapeutics, Medical Faculty, Heinrich-Heine University Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany

9. Gesine Kögler

   Heinrich Heine University Düsseldorf

   Affiliation as printed

   Institute for Transplantation Diagnostics and Cell Therapeutics, Medical Faculty, Heinrich-Heine University Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany

10. Marc D. Beyer

    University of Bonn · German Center for Neurodegenerative Diseases

    Affiliation as printed

    PRECISE Platform for Genomics and Epigenomics at German Center for Neurodegenerative Diseases (DZNE) and University of Bonn and West German Genome Center, Bonn, Germany; Immunogenomics & Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany

11. Markus Uhrberg corresponding

    Heinrich Heine University Düsseldorf

    Affiliation as printed

    Institute for Transplantation Diagnostics and Cell Therapeutics, Medical Faculty, Heinrich-Heine University Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany. Electronic address: markus.uhrberg@med.uni-duesseldorf.de