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Immune cell dynamics deconvoluted by single-cell RNA sequencing in normothermic machine perfusion of the liver

Author

Listed:
  • T. Hautz

    (Medical University of Innsbruck)

  • S. Salcher

    (Medical University of Innsbruck)

  • M. Fodor

    (Medical University of Innsbruck)

  • G. Sturm

    (Medical University of Innsbruck)

  • S. Ebner

    (Medical University of Innsbruck)

  • A. Mair

    (Medical University of Innsbruck)

  • M. Trebo

    (Medical University of Innsbruck)

  • G. Untergasser

    (Medical University of Innsbruck
    Tyrolpath Obrist Brunhuber GmbH)

  • S. Sopper

    (Medical University of Innsbruck)

  • B. Cardini

    (Medical University of Innsbruck)

  • A. Martowicz

    (Medical University of Innsbruck
    Tyrolpath Obrist Brunhuber GmbH)

  • J. Hofmann

    (Medical University of Innsbruck)

  • S. Daum

    (Medical University of Innsbruck)

  • M. Kalb

    (Medical University of Innsbruck)

  • T. Resch

    (Medical University of Innsbruck)

  • F. Krendl

    (Medical University of Innsbruck)

  • A. Weissenbacher

    (Medical University of Innsbruck)

  • G. Otarashvili

    (Medical University of Innsbruck)

  • P. Obrist

    (Tyrolpath Obrist Brunhuber GmbH)

  • B. Zelger

    (Medical University of Innsbruck)

  • D. Öfner

    (Medical University of Innsbruck)

  • Z. Trajanoski

    (Medical University of Innsbruck)

  • J. Troppmair

    (Medical University of Innsbruck)

  • R. Oberhuber

    (Medical University of Innsbruck)

  • A. Pircher

    (Medical University of Innsbruck)

  • D. Wolf

    (Medical University of Innsbruck)

  • S. Schneeberger

    (Medical University of Innsbruck)

Abstract

Normothermic machine perfusion (NMP) has emerged as an innovative organ preservation technique. Developing an understanding for the donor organ immune cell composition and its dynamic changes during NMP is essential. We aimed for a comprehensive characterization of immune cell (sub)populations, cell trafficking and cytokine release during liver NMP. Single-cell transcriptome profiling of human donor livers prior to, during NMP and after transplantation shows an abundance of CXC chemokine receptor 1+/2+ (CXCR1+/CXCR2+) neutrophils, which significantly decreased during NMP. This is paralleled by a large efflux of passenger leukocytes with neutrophil predominance in the perfusate. During NMP, neutrophils shift from a pro-inflammatory state towards an aged/chronically activated/exhausted phenotype, while anti-inflammatory/tolerogenic monocytes/macrophages are increased. We herein describe the dynamics of the immune cell repertoire, phenotypic immune cell shifts and a dominance of neutrophils during liver NMP, which potentially contribute to the inflammatory response. Our findings may serve as resource to initiate future immune-interventional studies.

Suggested Citation

  • T. Hautz & S. Salcher & M. Fodor & G. Sturm & S. Ebner & A. Mair & M. Trebo & G. Untergasser & S. Sopper & B. Cardini & A. Martowicz & J. Hofmann & S. Daum & M. Kalb & T. Resch & F. Krendl & A. Weisse, 2023. "Immune cell dynamics deconvoluted by single-cell RNA sequencing in normothermic machine perfusion of the liver," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37674-8
    DOI: 10.1038/s41467-023-37674-8
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    Cited by:

    1. Ngee-Soon Lau & Geoffrey McCaughan & Mark Ly & Ken Liu & Michael Crawford & Carlo Pulitano, 2024. "Long-term machine perfusion of human split livers: a new model for regenerative and translational research," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    2. Adam M. Thorne & Justina C. Wolters & Bianca Lascaris & Silke B. Bodewes & Veerle A. Lantinga & Otto B. Leeuwen & Iris E. M. Jong & Kirill Ustyantsev & Eugene Berezikov & Ton Lisman & Folkert Kuipers , 2023. "Bile proteome reveals biliary regeneration during normothermic preservation of human donor livers," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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