Multicytokine-producing CD4+ T cells characterize the livers of patients with NASH

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@article{5b4821b06b9c49618a3d45b3bd43af7e,
title = "Multicytokine-producing CD4+ T cells characterize the livers of patients with NASH",
abstract = "A role of CD4+ T cells during the progression from nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH) has been suggested, but which polarization state of these cells characterizes this progression and the development of fibrosis remain unclear. In addition, a gut-liver axis has been suggested to play a role in NASH, but the role of CD4+ T cells in this axis has just begun to be investigated. Combining single-cell RNA sequencing and multiple-parameter flow cytometry, we provide the first cell atlas to our knowledge focused on liver-infiltrating CD4+ T cells in patients with NAFLD and NASH, showing that NASH is characterized by a population of multicytokine-producing CD4+ T cells. Among these cells, only those with a Th17 polarization state were enriched in patients with advanced fibrosis. In parallel, we observed that Bacteroides appeared to be enriched in the intestine of NASH patients and to correlate with the frequency of multicytokine-producing CD4+ T cells. In short, we deliver a CD4+ T cell atlas of NAFLD and NASH, providing the rationale to target CD4+ T cells with a Th17 polarization state to block fibrosis development. Finally, our data offer an early indication to test whether multicytokine-producing CD4+ T cells are part of the gut-liver axis characterizing NASH.",
keywords = "Humans, Non-alcoholic Fatty Liver Disease, CD4-Positive T-Lymphocytes, Fibrosis",
author = "Anna Woestemeier and Pasquale Scognamiglio and Yu Zhao and Jonas Wagner and Franziska Muscate and Christian Casar and Francesco Siracusa and Filippo Cortesi and Theodora Agalioti and Simone M{\"u}ller and Adrian Sagebiel and Leonie Konczalla and Ramez Wahib and Karl-Frederick Karstens and Giannou, {Anastasios D} and Anna Dupr{\'e}e and Stefan Wolter and Wong, {Milagros N} and M{\"u}hlig, {Anne K} and Bielecka, {Agata A} and Vikas Bansal and Tianran Zhang and Oliver Mann and Puelles, {Victor G} and Huber, {Tobias B} and Lohse, {Ansgar W} and Izbicki, {Jakob R} and Palm, {Noah W} and Stefan Bonn and Samuel Huber and Nicola Gagliani",
year = "2023",
month = jan,
day = "10",
doi = "10.1172/jci.insight.153831",
language = "English",
volume = "8",
journal = "JCI INSIGHT",
issn = "2379-3708",
publisher = "The American Society for Clinical Investigation",
number = "1",

}

RIS

TY - JOUR

T1 - Multicytokine-producing CD4+ T cells characterize the livers of patients with NASH

AU - Woestemeier, Anna

AU - Scognamiglio, Pasquale

AU - Zhao, Yu

AU - Wagner, Jonas

AU - Muscate, Franziska

AU - Casar, Christian

AU - Siracusa, Francesco

AU - Cortesi, Filippo

AU - Agalioti, Theodora

AU - Müller, Simone

AU - Sagebiel, Adrian

AU - Konczalla, Leonie

AU - Wahib, Ramez

AU - Karstens, Karl-Frederick

AU - Giannou, Anastasios D

AU - Duprée, Anna

AU - Wolter, Stefan

AU - Wong, Milagros N

AU - Mühlig, Anne K

AU - Bielecka, Agata A

AU - Bansal, Vikas

AU - Zhang, Tianran

AU - Mann, Oliver

AU - Puelles, Victor G

AU - Huber, Tobias B

AU - Lohse, Ansgar W

AU - Izbicki, Jakob R

AU - Palm, Noah W

AU - Bonn, Stefan

AU - Huber, Samuel

AU - Gagliani, Nicola

PY - 2023/1/10

Y1 - 2023/1/10

N2 - A role of CD4+ T cells during the progression from nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH) has been suggested, but which polarization state of these cells characterizes this progression and the development of fibrosis remain unclear. In addition, a gut-liver axis has been suggested to play a role in NASH, but the role of CD4+ T cells in this axis has just begun to be investigated. Combining single-cell RNA sequencing and multiple-parameter flow cytometry, we provide the first cell atlas to our knowledge focused on liver-infiltrating CD4+ T cells in patients with NAFLD and NASH, showing that NASH is characterized by a population of multicytokine-producing CD4+ T cells. Among these cells, only those with a Th17 polarization state were enriched in patients with advanced fibrosis. In parallel, we observed that Bacteroides appeared to be enriched in the intestine of NASH patients and to correlate with the frequency of multicytokine-producing CD4+ T cells. In short, we deliver a CD4+ T cell atlas of NAFLD and NASH, providing the rationale to target CD4+ T cells with a Th17 polarization state to block fibrosis development. Finally, our data offer an early indication to test whether multicytokine-producing CD4+ T cells are part of the gut-liver axis characterizing NASH.

AB - A role of CD4+ T cells during the progression from nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH) has been suggested, but which polarization state of these cells characterizes this progression and the development of fibrosis remain unclear. In addition, a gut-liver axis has been suggested to play a role in NASH, but the role of CD4+ T cells in this axis has just begun to be investigated. Combining single-cell RNA sequencing and multiple-parameter flow cytometry, we provide the first cell atlas to our knowledge focused on liver-infiltrating CD4+ T cells in patients with NAFLD and NASH, showing that NASH is characterized by a population of multicytokine-producing CD4+ T cells. Among these cells, only those with a Th17 polarization state were enriched in patients with advanced fibrosis. In parallel, we observed that Bacteroides appeared to be enriched in the intestine of NASH patients and to correlate with the frequency of multicytokine-producing CD4+ T cells. In short, we deliver a CD4+ T cell atlas of NAFLD and NASH, providing the rationale to target CD4+ T cells with a Th17 polarization state to block fibrosis development. Finally, our data offer an early indication to test whether multicytokine-producing CD4+ T cells are part of the gut-liver axis characterizing NASH.

KW - Humans

KW - Non-alcoholic Fatty Liver Disease

KW - CD4-Positive T-Lymphocytes

KW - Fibrosis

U2 - 10.1172/jci.insight.153831

DO - 10.1172/jci.insight.153831

M3 - SCORING: Journal article

C2 - 36625344

VL - 8

JO - JCI INSIGHT

JF - JCI INSIGHT

SN - 2379-3708

IS - 1

M1 - e153831

ER -