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

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 Weissenbacher; G Otarashvili; P Obrist; B Zelger; D Öfner; Z Trajanoski; J Troppmair; R Oberhuber; A Pircher; D Wolf; S Schneeberger

doi:10.1038/s41467-023-37674-8

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

Nat Commun. 2023 Apr 21;14(1):2285. doi: 10.1038/s41467-023-37674-8.

Authors

T Hautz^#¹, S Salcher^#², M Fodor^#¹, G Sturm³, S Ebner¹, A Mair², M Trebo², G Untergasser^{2

4}, S Sopper², B Cardini¹, A Martowicz^{2

4}, J Hofmann¹, S Daum², M Kalb², T Resch¹, F Krendl¹, A Weissenbacher¹, G Otarashvili¹, P Obrist⁴, B Zelger⁵, D Öfner¹, Z Trajanoski³, J Troppmair¹, R Oberhuber¹, A Pircher², D Wolf⁶, S Schneeberger⁷

Affiliations

¹ Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, organLife Laboratory and D. Swarovski Research Laboratory, Medical University of Innsbruck, Innsbruck, Austria.
² Department of Internal Medicine V, Hematology and Oncology, Comprehensive Cancer Center Innsbruck (CCCI), Medical University of Innsbruck, Innsbruck, Austria.
³ Institute of Bioinformatics, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
⁴ Tyrolpath Obrist Brunhuber GmbH, Zams, Austria.
⁵ Institute of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, Innsbruck, Austria.
⁶ Department of Internal Medicine V, Hematology and Oncology, Comprehensive Cancer Center Innsbruck (CCCI), Medical University of Innsbruck, Innsbruck, Austria. dominik.wolf@i-med.ac.at.
⁷ Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, organLife Laboratory and D. Swarovski Research Laboratory, Medical University of Innsbruck, Innsbruck, Austria. stefan.schneeberger@i-med.ac.at.

^# Contributed equally.

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.

Publication types

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

MeSH terms

Aged
Humans
Liver
Liver Transplantation* / methods
Organ Preservation / methods
Perfusion / methods
Sequence Analysis, RNA