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Inflammatory type 2 conventional dendritic cells contribute to murine and human cholangitis

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Inflammatory type 2 conventional dendritic cells contribute to murine and human cholangitis. / Müller, Anna-Lena; Casar, Christian; Preti, Max; Krzikalla, Daria; Gottwick, Cornelia; Averhoff, Pia; Rosenstiel, Philip; Gelderblom, Mathias; Altfeld, Marcus; Lohse, Ansgar W; Steinmann, Silja; Sebode, Marcial; Krause, Jenny; Schwinge, Dorothee; Schramm, Christoph; Carambia, Antonella; Herkel, Johannes.

In: J HEPATOL, Vol. 77, No. 6, 12.2022, p. 1532-1544.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Müller, A-L, Casar, C, Preti, M, Krzikalla, D, Gottwick, C, Averhoff, P, Rosenstiel, P, Gelderblom, M, Altfeld, M, Lohse, AW, Steinmann, S, Sebode, M, Krause, J, Schwinge, D, Schramm, C, Carambia, A & Herkel, J 2022, 'Inflammatory type 2 conventional dendritic cells contribute to murine and human cholangitis', J HEPATOL, vol. 77, no. 6, pp. 1532-1544. https://doi.org/10.1016/j.jhep.2022.06.025

APA

Müller, A-L., Casar, C., Preti, M., Krzikalla, D., Gottwick, C., Averhoff, P., Rosenstiel, P., Gelderblom, M., Altfeld, M., Lohse, A. W., Steinmann, S., Sebode, M., Krause, J., Schwinge, D., Schramm, C., Carambia, A., & Herkel, J. (2022). Inflammatory type 2 conventional dendritic cells contribute to murine and human cholangitis. J HEPATOL, 77(6), 1532-1544. https://doi.org/10.1016/j.jhep.2022.06.025

Vancouver

Müller A-L, Casar C, Preti M, Krzikalla D, Gottwick C, Averhoff P et al. Inflammatory type 2 conventional dendritic cells contribute to murine and human cholangitis. J HEPATOL. 2022 Dec;77(6):1532-1544. https://doi.org/10.1016/j.jhep.2022.06.025

Bibtex

@article{76b65f81bd6a4b5f89f6810885fcf28b,
title = "Inflammatory type 2 conventional dendritic cells contribute to murine and human cholangitis",
abstract = "BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is a progressive cholangiopathy characterised by fibrotic stricturing and inflammation of bile ducts, which seems to be driven by a maladaptive immune response to bile duct injury. The histological finding of dendritic cell expansion in portal fields of patients with PSC prompted us to investigate the role of dendritic cells in orchestrating the immune response to bile duct injury.METHODS: Dendritic cell numbers and subtypes were determined in different mouse models of cholangitis by flow cytometry based on lineage-imprinted markers. Findings were confirmed by immunofluorescence microscopy of murine livers, and liver samples from patients with PSC were compared to control samples from bariatric surgery patients. Using genetic tools, selected dendritic cell subsets were depleted in murine cholangitis. The dendritic cell response to bile duct injury was determined by single-cell transcriptomics.RESULTS: Cholangitis mouse models were characterised by selective intrahepatic expansion of type 2 conventional dendritic cells, whereas plasmacytoid and type 1 conventional dendritic cells were not expanded. Expansion of type 2 conventional dendritic cells in human PSC lesions was confirmed by histology. Depletion studies revealed a proinflammatory role of type 2 conventional dendritic cells. Single-cell transcriptomics confirmed inflammatory maturation of the intrahepatic type 2 conventional dendritic cells and identified dendritic cell-derived inflammatory mediators.CONCLUSIONS: Cholangitis is characterised by intrahepatic expansion and inflammatory maturation of type 2 conventional dendritic cells in response to biliary injury. Therefore, type 2 conventional dendritic cells and their inflammatory mediators might be potential therapeutic targets for the treatment of PSC.LAY SUMMARY: Primary sclerosing cholangitis (PSC) is an inflammatory liver disease of the bile ducts for which there is no effective treatment. Herein, we show that the inflammatory immune response to bile duct injury is organised by a specific subtype of immune cell called conventional type 2 dendritic cells. Our findings suggest that this cell subtype and the inflammatory molecules it produces are potential therapeutic targets for PSC.",
author = "Anna-Lena M{\"u}ller and Christian Casar and Max Preti and Daria Krzikalla and Cornelia Gottwick and Pia Averhoff and Philip Rosenstiel and Mathias Gelderblom and Marcus Altfeld and Lohse, {Ansgar W} and Silja Steinmann and Marcial Sebode and Jenny Krause and Dorothee Schwinge and Christoph Schramm and Antonella Carambia and Johannes Herkel",
note = "Copyright {\textcopyright} 2022 The Authors. Published by Elsevier B.V. All rights reserved.",
year = "2022",
month = dec,
doi = "10.1016/j.jhep.2022.06.025",
language = "English",
volume = "77",
pages = "1532--1544",
journal = "J HEPATOL",
issn = "0168-8278",
publisher = "Elsevier",
number = "6",

}

RIS

TY - JOUR

T1 - Inflammatory type 2 conventional dendritic cells contribute to murine and human cholangitis

AU - Müller, Anna-Lena

AU - Casar, Christian

AU - Preti, Max

AU - Krzikalla, Daria

AU - Gottwick, Cornelia

AU - Averhoff, Pia

AU - Rosenstiel, Philip

AU - Gelderblom, Mathias

AU - Altfeld, Marcus

AU - Lohse, Ansgar W

AU - Steinmann, Silja

AU - Sebode, Marcial

AU - Krause, Jenny

AU - Schwinge, Dorothee

AU - Schramm, Christoph

AU - Carambia, Antonella

AU - Herkel, Johannes

N1 - Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.

PY - 2022/12

Y1 - 2022/12

N2 - BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is a progressive cholangiopathy characterised by fibrotic stricturing and inflammation of bile ducts, which seems to be driven by a maladaptive immune response to bile duct injury. The histological finding of dendritic cell expansion in portal fields of patients with PSC prompted us to investigate the role of dendritic cells in orchestrating the immune response to bile duct injury.METHODS: Dendritic cell numbers and subtypes were determined in different mouse models of cholangitis by flow cytometry based on lineage-imprinted markers. Findings were confirmed by immunofluorescence microscopy of murine livers, and liver samples from patients with PSC were compared to control samples from bariatric surgery patients. Using genetic tools, selected dendritic cell subsets were depleted in murine cholangitis. The dendritic cell response to bile duct injury was determined by single-cell transcriptomics.RESULTS: Cholangitis mouse models were characterised by selective intrahepatic expansion of type 2 conventional dendritic cells, whereas plasmacytoid and type 1 conventional dendritic cells were not expanded. Expansion of type 2 conventional dendritic cells in human PSC lesions was confirmed by histology. Depletion studies revealed a proinflammatory role of type 2 conventional dendritic cells. Single-cell transcriptomics confirmed inflammatory maturation of the intrahepatic type 2 conventional dendritic cells and identified dendritic cell-derived inflammatory mediators.CONCLUSIONS: Cholangitis is characterised by intrahepatic expansion and inflammatory maturation of type 2 conventional dendritic cells in response to biliary injury. Therefore, type 2 conventional dendritic cells and their inflammatory mediators might be potential therapeutic targets for the treatment of PSC.LAY SUMMARY: Primary sclerosing cholangitis (PSC) is an inflammatory liver disease of the bile ducts for which there is no effective treatment. Herein, we show that the inflammatory immune response to bile duct injury is organised by a specific subtype of immune cell called conventional type 2 dendritic cells. Our findings suggest that this cell subtype and the inflammatory molecules it produces are potential therapeutic targets for PSC.

AB - BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is a progressive cholangiopathy characterised by fibrotic stricturing and inflammation of bile ducts, which seems to be driven by a maladaptive immune response to bile duct injury. The histological finding of dendritic cell expansion in portal fields of patients with PSC prompted us to investigate the role of dendritic cells in orchestrating the immune response to bile duct injury.METHODS: Dendritic cell numbers and subtypes were determined in different mouse models of cholangitis by flow cytometry based on lineage-imprinted markers. Findings were confirmed by immunofluorescence microscopy of murine livers, and liver samples from patients with PSC were compared to control samples from bariatric surgery patients. Using genetic tools, selected dendritic cell subsets were depleted in murine cholangitis. The dendritic cell response to bile duct injury was determined by single-cell transcriptomics.RESULTS: Cholangitis mouse models were characterised by selective intrahepatic expansion of type 2 conventional dendritic cells, whereas plasmacytoid and type 1 conventional dendritic cells were not expanded. Expansion of type 2 conventional dendritic cells in human PSC lesions was confirmed by histology. Depletion studies revealed a proinflammatory role of type 2 conventional dendritic cells. Single-cell transcriptomics confirmed inflammatory maturation of the intrahepatic type 2 conventional dendritic cells and identified dendritic cell-derived inflammatory mediators.CONCLUSIONS: Cholangitis is characterised by intrahepatic expansion and inflammatory maturation of type 2 conventional dendritic cells in response to biliary injury. Therefore, type 2 conventional dendritic cells and their inflammatory mediators might be potential therapeutic targets for the treatment of PSC.LAY SUMMARY: Primary sclerosing cholangitis (PSC) is an inflammatory liver disease of the bile ducts for which there is no effective treatment. Herein, we show that the inflammatory immune response to bile duct injury is organised by a specific subtype of immune cell called conventional type 2 dendritic cells. Our findings suggest that this cell subtype and the inflammatory molecules it produces are potential therapeutic targets for PSC.

U2 - 10.1016/j.jhep.2022.06.025

DO - 10.1016/j.jhep.2022.06.025

M3 - SCORING: Journal article

C2 - 35798133

VL - 77

SP - 1532

EP - 1544

JO - J HEPATOL

JF - J HEPATOL

SN - 0168-8278

IS - 6

ER -