Myeloid spatial and transcriptional molecular signature of ischemia-reperfusion injury in human liver transplantation.

Autor:	Sosa RA; Depertment of Pathology and Laboratory Medicine, UCLA, Los Angeles, California, USA.; Department of Pathology and Laboratory Medicine, UCLA Immunogenetics Center, UCLA, Los Angeles, California, USA., Ahn R; Institute for Quantitative and Computational Biosciences, UCLA, Los Angeles, California, USA.; Depertment of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, California, USA., Li F; Depertment of Pathology and Laboratory Medicine, UCLA, Los Angeles, California, USA., Terry AQ; Depertment of Pathology and Laboratory Medicine, UCLA, Los Angeles, California, USA., Qian Z; Institute for Quantitative and Computational Biosciences, UCLA, Los Angeles, California, USA., Bhat A; Depertment of Pathology and Laboratory Medicine, UCLA, Los Angeles, California, USA., Sen S; Depertment of Pathology and Laboratory Medicine, UCLA, Los Angeles, California, USA., Naini BV; Depertment of Pathology and Laboratory Medicine, UCLA, Los Angeles, California, USA., Ito T; Depertment of Surgery, UCLA, Los Angeles, California, USA., Kaldas FM; Depertment of Surgery, UCLA, Los Angeles, California, USA., Hoffmann A; Institute for Quantitative and Computational Biosciences, UCLA, Los Angeles, California, USA.; Depertment of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, California, USA., Busuttil RW; Depertment of Surgery, UCLA, Los Angeles, California, USA., Kupiec-Weglinski JW; Depertment of Pathology and Laboratory Medicine, UCLA, Los Angeles, California, USA.; Depertment of Surgery, UCLA, Los Angeles, California, USA., Gjertson DW; Depertment of Pathology and Laboratory Medicine, UCLA, Los Angeles, California, USA.; Department of Pathology and Laboratory Medicine, UCLA Immunogenetics Center, UCLA, Los Angeles, California, USA., Reed EF; Depertment of Pathology and Laboratory Medicine, UCLA, Los Angeles, California, USA.; Department of Pathology and Laboratory Medicine, UCLA Immunogenetics Center, UCLA, Los Angeles, California, USA.
Jazyk:	angličtina
Zdroj:	Hepatology communications [Hepatol Commun] 2024 Jan 11; Vol. 8 (1). Date of Electronic Publication: 2024 Jan 11 (Print Publication: 2024).
DOI:	10.1097/HC9.0000000000000330
Abstrakt:	Background: Ischemia-reperfusion injury (IRI) is a significant clinical concern in liver transplantation, with a key influence on short-term and long-term allograft and patient survival. Myeloid cells trigger and sustain tissue inflammation and damage associated with IRI, but the mechanisms regulating these activities are unknown. To address this, we investigated the molecular characteristics of intragraft myeloid cells present in biopsy-proven IRI- and IRI+ liver transplants. Methods: RNA-sequencing was performed on 80 pre-reperfusion and post-reperfusion biopsies from 40 human recipients of liver transplantation (23 IRI+, 17 IRI-). We used transcriptional profiling and computational approaches to identify specific gene coexpression network modules correlated with functional subsets of MPO+, lysozyme+, and CD68+ myeloid cells quantified by immunohistochemistry on sequential sections from the same patient biopsies. Results: A global molecular map showed gene signatures related to myeloid activation in all patients regardless of IRI status; however, myeloid cell subsets differed dramatically in their spatial morphology and associated gene signatures. IRI- recipients were found to have a natural corticosteroid production and response profile from pre-reperfusion to post-reperfusion, particularly among monocytes/macrophages. The pre-reperfusion signature of IRI+ recipients included acute inflammatory responses in neutrophils and increased translation of adaptive immune-related genes in monocytes/macrophages coupled with decreased glucocorticoid responses. Subsequent lymphocyte activation at post-reperfusion identified transcriptional programs associated with the transition to adaptive immunity found only among IRI+ recipients. Conclusions: Myeloid subset-specific genes and related signaling pathways provide targets for the development of therapeutic strategies aimed at limiting IRI in the clinical setting of liver transplantation. (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)
Databáze:	MEDLINE
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