Single-cell RNA sequencing identifies a population of human liver-type ILC1s

Benjamin Krämer; Ansel P Nalin; Feiyang Ma; Sarah Eickhoff; Philipp Lutz; Sonia Leonardelli; Felix Goeser; Claudia Finnemann; Gudrun Hack; Jan Raabe; Michael ToVinh; Sarah Ahmad; Christoph Hoffmeister; Kim M Kaiser; Steffen Manekeller; Vittorio Branchi; Tobias Bald; Michael Hölzel; Robert Hüneburg; Hans Dieter Nischalke; Alexander Semaan; Bettina Langhans; Dominik J Kaczmarek; Brooke Benner; Matthew R Lordo; Jesse Kowalski; Adam Gerhardt; Jörg Timm; Marieta Toma; Raphael Mohr; Andreas Türler; Arthur Charpentier; Tobias van Bremen; Georg Feldmann; Arne Sattler; Katja Kotsch; Ali T Abdallah; Christian P Strassburg; Ulrich Spengler; William E Carson 3rd; Bethany L Mundy-Bosse; Matteo Pellegrini; Timothy E O'Sullivan; Aharon G Freud; Jacob Nattermann

doi:10.1016/j.celrep.2022.111937

Single-cell RNA sequencing identifies a population of human liver-type ILC1s

Cell Rep. 2023 Jan 31;42(1):111937. doi: 10.1016/j.celrep.2022.111937. Epub 2023 Jan 1.

Authors

Benjamin Krämer¹, Ansel P Nalin², Feiyang Ma³, Sarah Eickhoff⁴, Philipp Lutz⁵, Sonia Leonardelli⁴, Felix Goeser⁵, Claudia Finnemann⁵, Gudrun Hack⁵, Jan Raabe⁵, Michael ToVinh⁵, Sarah Ahmad⁵, Christoph Hoffmeister⁵, Kim M Kaiser⁵, Steffen Manekeller⁶, Vittorio Branchi⁶, Tobias Bald⁴, Michael Hölzel⁴, Robert Hüneburg⁷, Hans Dieter Nischalke⁷, Alexander Semaan⁶, Bettina Langhans⁵, Dominik J Kaczmarek⁷, Brooke Benner⁸, Matthew R Lordo², Jesse Kowalski⁹, Adam Gerhardt¹⁰, Jörg Timm¹¹, Marieta Toma¹², Raphael Mohr⁷, Andreas Türler¹³, Arthur Charpentier¹⁴, Tobias van Bremen¹⁵, Georg Feldmann¹⁶, Arne Sattler¹⁷, Katja Kotsch¹⁷, Ali T Abdallah¹⁸, Christian P Strassburg⁷, Ulrich Spengler⁵, William E Carson 3rd¹⁹, Bethany L Mundy-Bosse²⁰, Matteo Pellegrini³, Timothy E O'Sullivan²¹, Aharon G Freud²², Jacob Nattermann⁵

Affiliations

¹ Department of Internal Medicine I, University of Bonn, 53127 Bonn, Germany; German Center for Infection Research (DZIF), 53127 Bonn, Germany. Electronic address: benjamin.kraemer@ukbonn.de.
² Medical Scientist Training Program, The Ohio State University, Columbus, OH 43210, USA; Biomedical Sciences Graduate Program, The Ohio State University, Columbus, OH 43210, USA.
³ Molecular Cell and Developmental Biology, College of Life Sciences, University of California Los Angeles, Los Angeles, CA 90095, USA.
⁴ Institute of Experimental Oncology (IEO), Medical Faculty, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany.
⁵ Department of Internal Medicine I, University of Bonn, 53127 Bonn, Germany; German Center for Infection Research (DZIF), 53127 Bonn, Germany.
⁶ Department of Surgery, University of Bonn, 53127 Bonn, Germany.
⁷ Department of Internal Medicine I, University of Bonn, 53127 Bonn, Germany.
⁸ Biomedical Sciences Graduate Program, The Ohio State University, Columbus, OH 43210, USA.
⁹ Nationwide Children's Hospital, Columbus, OH, USA.
¹⁰ College of Medicine, University of Cincinnati, Cincinnati, OH 45221, USA.
¹¹ Institute of Virology, University of Duesseldorf, 40225 Düsseldorf, Germany.
¹² Department of Pathology, University of Bonn, 53127 Bonn, Germany.
¹³ General and Visceral Surgery, Johanniter Hospital, 53113 Bonn, Germany.
¹⁴ Department of Otorhinolaryngology/Head and Neck Surgery, University of Bonn, 53127 Bonn, Germany; Department of Otorhinolaryngology, Head and Neck Surgery, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
¹⁵ Department of Otorhinolaryngology/Head and Neck Surgery, University of Bonn, 53127 Bonn, Germany.
¹⁶ Department of Internal Medicine III, University of Bonn, 53127 Bonn, Germany.
¹⁷ Clinic for Surgery, Transplant Immunology Lab, Charité University Hospital Berlin, 10117 Berlin, Germany.
¹⁸ Interdisciplinary Center for Clinical Research, RWTH Aachen University, 52074 Aachen, Germany.
¹⁹ Division of Surgical Oncology, Department of Surgery, Comprehensive Cancer Center and The James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, USA.
²⁰ Division of Hematology, Department of Internal Medicine, Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA.
²¹ Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 900953, USA.
²² Department of Pathology, Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA. Electronic address: aharon.freud@osumc.edu.

Abstract

Group 1 innate lymphoid cells (ILCs) comprise a heterogeneous family of cytotoxic natural killer (NK) cells and ILC1s. We identify a population of "liver-type" ILC1s with transcriptional, phenotypic, and functional features distinct from those of conventional and liver-resident NK cells as well as from other previously described human ILC1 subsets. LT-ILC1s are CD49a⁺CD94⁺CD200R1⁺, express the transcription factor T-BET, and do not express the activating receptor NKp80 or the transcription factor EOMES. Similar to NK cells, liver-type ILC1s produce IFN-γ, TNF-α, and GM-CSF; however, liver-type ILC1s also produce IL-2 and lack perforin and granzyme-B. Liver-type ILC1s are expanded in cirrhotic liver tissues, and they can be produced from blood-derived ILC precursors in vitro in the presence of TGF-β1 and liver sinusoidal endothelial cells. Cells with similar signature and function can also be found in tonsil and intestinal tissues. Collectively, our study identifies and classifies a population of human cross-tissue ILC1s.

Keywords: CP: Immunology; ILC1; TGF-β; cirrhotic liver; cross-tissue ILC1; human group 1 ILC; innate lymphoid cell; liver ILC1; liver environment; natural killer cell.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Endothelial Cells
Humans
Immunity, Innate*
Killer Cells, Natural
Liver
Lymphocytes*
Sequence Analysis, RNA
Transcription Factors

Substances

Transcription Factors

Abstract

Publication types

MeSH terms

Substances

Grants and funding