Single-cell atlas of hepatic T cells reveals expansion of liver-resident naive-like CD4

Atlas Immune-mediated liver disease Naive T cells Primary Sclerosing Cholangitis Single-cell sequencing T cells T(H)17 cells Tissue residency

Journal

Journal of hepatology
ISSN: 1600-0641
Titre abrégé: J Hepatol
Pays: Netherlands
ID NLM: 8503886

Informations de publication

Date de publication:
08 2021
Historique:
received: 10 08 2020
revised: 16 02 2021
accepted: 17 03 2021
pubmed: 29 3 2021
medline: 8 2 2022
entrez: 28 3 2021
Statut: ppublish

Résumé

Little is known about the composition of intrahepatic immune cells and their contribution to the pathogenesis of primary sclerosing cholangitis (PSC). Herein, we aimed to create an atlas of intrahepatic T cells and thereby perform an in-depth characterization of T cells in inflamed human liver. Different single-cell RNA sequencing methods were combined with in silico analyses on intrahepatic and peripheral T cells from patients with PSC (n = 11) and healthy donors (HDs, n = 4). Multi-parameter flow cytometry and functional in vitro experiments were conducted on samples from patients with PSC (n = 24), controls with other liver diseases and HDs. We identified a population of intrahepatic naive-like CD4 We report the first atlas of intrahepatic T cells in PSC, which led to the identification of a previously unrecognized population of tissue-resident naive-like T cells in the inflamed human liver and to the finding that naive CD4 The composition of intrahepatic immune cells in primary sclerosing cholangitis (PSC) and their contribution to disease pathogenesis is widely unknown. We analysed intrahepatic T cells and identified a previously uncharacterized population of liver-resident CD4

Sections du résumé

BACKGROUND & AIMS
Little is known about the composition of intrahepatic immune cells and their contribution to the pathogenesis of primary sclerosing cholangitis (PSC). Herein, we aimed to create an atlas of intrahepatic T cells and thereby perform an in-depth characterization of T cells in inflamed human liver.
METHODS
Different single-cell RNA sequencing methods were combined with in silico analyses on intrahepatic and peripheral T cells from patients with PSC (n = 11) and healthy donors (HDs, n = 4). Multi-parameter flow cytometry and functional in vitro experiments were conducted on samples from patients with PSC (n = 24), controls with other liver diseases and HDs.
RESULTS
We identified a population of intrahepatic naive-like CD4
CONCLUSION
We report the first atlas of intrahepatic T cells in PSC, which led to the identification of a previously unrecognized population of tissue-resident naive-like T cells in the inflamed human liver and to the finding that naive CD4
LAY SUMMARY
The composition of intrahepatic immune cells in primary sclerosing cholangitis (PSC) and their contribution to disease pathogenesis is widely unknown. We analysed intrahepatic T cells and identified a previously uncharacterized population of liver-resident CD4

Identifiants

pubmed: 33774059
pii: S0168-8278(21)00219-1
doi: 10.1016/j.jhep.2021.03.016
pmc: PMC8310924
pii:
doi:

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

414-423

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest The authors declare no conflict of interest. Please refer to the accompanying ICMJE disclosure forms for further details.

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Auteurs

Tobias Poch (T)

I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246 Germany.

Jenny Krause (J)

I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246 Germany.

Christian Casar (C)

I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246 Germany; Bioinformatics Core, University Medical Center Hamburg-Eppendorf, Hamburg 20246 Germany.

Timur Liwinski (T)

I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246 Germany; Immunology Department, Weizmann Institute of Science, Rehovot 7610001 Israel.

Laura Glau (L)

Institute of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg 20246 Germany.

Max Kaufmann (M)

Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg 20246 Germany.

Annika E Ahrenstorf (AE)

Virus Immunology Department, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg 20246 Germany.

Leonard U Hess (LU)

Virus Immunology Department, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg 20246 Germany.

Annerose E Ziegler (AE)

Virus Immunology Department, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg 20246 Germany.

Glòria Martrus (G)

Virus Immunology Department, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg 20246 Germany.

Sebastian Lunemann (S)

Virus Immunology Department, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg 20246 Germany.

Marcial Sebode (M)

I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246 Germany.

Jun Li (J)

Department for General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg 20246 Germany.

Dorothee Schwinge (D)

I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246 Germany.

Christian F Krebs (CF)

III. Department of Medicine, Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg 20246 Germany; Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg 20246 Germany.

Andre Franke (A)

Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel 24105 Germany.

Manuel A Friese (MA)

Institute of Neuroimmunology and Multiple Sclerosis, University Medical Center Hamburg-Eppendorf, Hamburg 20246 Germany.

Karl J Oldhafer (KJ)

Department of General and Abdominal Surgery, Asklepios Hospital Barmbek, Semmelweis University of Medicine Hamburg, Germany.

Lutz Fischer (L)

Department for Visceral Transplant Surgery, University Medical Center Hamburg-Eppendorf, Hamburg 20246 Germany.

Marcus Altfeld (M)

Institute of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg 20246 Germany; Virus Immunology Department, Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg 20246 Germany.

Ansgar W Lohse (AW)

I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246 Germany; Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg 20246 Germany.

Samuel Huber (S)

I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246 Germany; Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg 20246 Germany.

Eva Tolosa (E)

Institute of Immunology, University Medical Center Hamburg-Eppendorf, Hamburg 20246 Germany.

Nicola Gagliani (N)

I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246 Germany; Department for General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg 20246 Germany; Immunology and Allergy Unit, Department of Medicine Solna, Karolinska Institute, Stockholm 17177 Sweden. Electronic address: n.gagliani@uke.de.

Christoph Schramm (C)

I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246 Germany; Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg 20246 Germany; Martin Zeitz Center for Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg 20246 Germany. Electronic address: c.schramm@uke.de.

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Classifications MeSH