Identification and characterization of a hepatic IL-13-producing ILC3-like population potentially involved in liver fibrosis

Copyright © 2023 American Association for the Study of Liver Diseases..

BACKGROUND AND AIMS: Human innate lymphoid cells (ILCs) are critically involved in the modulation of homeostatic and inflammatory processes in various tissues. However, only little is known about the composition of the intrahepatic ILC pool and its potential role in chronic liver disease. Here, we performed a detailed characterization of intrahepatic ILCs in both healthy and fibrotic livers.

APPROACH AND RESULTS: A total of 50 livers (nonfibrotic = 22, and fibrotic = 29) were analyzed and compared with colon and tonsil tissue (each N = 14) and peripheral blood (N = 32). Human intrahepatic ILCs were characterized ex vivo and on stimulation using flow cytometry and single-cell RNA sequencing. ILC differentiation and plasticity were analyzed by both bulk and clonal expansion experiments. Finally, the effects of ILC-derived cytokines on primary human HSteCs were studied. Unexpectedly, we found that an "unconventional" ILC3-like cell represented the major IL-13-producing liver ILC subset. IL-13 + ILC3-like cells were specifically enriched in the human liver, and increased frequencies of this cell type were found in fibrotic livers. ILC3-derived IL-13 production induced upregulation of proinflammatory genes in HSteCs, indicating a potential role in the regulation of hepatic fibrogenesis. Finally, we identified KLRG1-expressing ILC precursors as the potential progenitor of hepatic IL-13 + ILC3-like cells.

CONCLUSIONS: We identified a formerly undescribed subset of IL-13-producing ILC3-like cells that is enriched in the human liver and may be involved in the modulation of chronic liver disease.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:78

Enthalten in:

Hepatology (Baltimore, Md.) - 78(2023), 3 vom: 01. Sept., Seite 787-802

Sprache:

Englisch

Beteiligte Personen:

Raabe, Jan [VerfasserIn]
Kaiser, Kim M [VerfasserIn]
ToVinh, Michael [VerfasserIn]
Finnemann, Claudia [VerfasserIn]
Lutz, Philipp [VerfasserIn]
Hoffmeister, Christoph [VerfasserIn]
Bischoff, Jenny [VerfasserIn]
Goeser, Felix [VerfasserIn]
Kaczmarek, Dominik J [VerfasserIn]
Glowka, Tim R [VerfasserIn]
Manekeller, Steffen [VerfasserIn]
Charpentier, Arthur [VerfasserIn]
Langhans, Bettina [VerfasserIn]
Nischalke, Hans Dieter [VerfasserIn]
Toma, Marieta [VerfasserIn]
Strassburg, Christian P [VerfasserIn]
Spengler, Ulrich [VerfasserIn]
Abdallah, Ali T [VerfasserIn]
Krämer, Benjamin [VerfasserIn]
Nattermann, Jacob [VerfasserIn]

Links:

Volltext

Themen:

Interleukin-13
Journal Article
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 21.08.2023

Date Revised 16.01.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1097/HEP.0000000000000350

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM35533741X