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Integrative Omics Analysis Unravels Microvascular Inflammation-Related Pathways in Kidney Allograft Biopsies

In solid-organ transplantation, microRNAs (miRNAs) have emerged as key players in the regulation of allograft cells function in response to injury. To gain insight into the role of miRNAs in antibody-mediated rejection, a rejection phenotype histologically defined by microvascular inflammation, kidn...

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Autores principales: Tinel, Claire, Lamarthée, Baptiste, Callemeyn, Jasper, Van Loon, Elisabet, Sauvaget, Virginia, Morin, Lise, Aouni, Laïla, Rabant, Marion, Gwinner, Wilfried, Marquet, Pierre, Naesens, Maarten, Anglicheau, Dany
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8593247/
https://www.ncbi.nlm.nih.gov/pubmed/34795664
http://dx.doi.org/10.3389/fimmu.2021.738795
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author Tinel, Claire
Lamarthée, Baptiste
Callemeyn, Jasper
Van Loon, Elisabet
Sauvaget, Virginia
Morin, Lise
Aouni, Laïla
Rabant, Marion
Gwinner, Wilfried
Marquet, Pierre
Naesens, Maarten
Anglicheau, Dany
author_facet Tinel, Claire
Lamarthée, Baptiste
Callemeyn, Jasper
Van Loon, Elisabet
Sauvaget, Virginia
Morin, Lise
Aouni, Laïla
Rabant, Marion
Gwinner, Wilfried
Marquet, Pierre
Naesens, Maarten
Anglicheau, Dany
author_sort Tinel, Claire
collection PubMed
description In solid-organ transplantation, microRNAs (miRNAs) have emerged as key players in the regulation of allograft cells function in response to injury. To gain insight into the role of miRNAs in antibody-mediated rejection, a rejection phenotype histologically defined by microvascular inflammation, kidney allograft biopsies were subjected to miRNA but also messenger RNA (mRNA) profiling. Using a unique multistep selection process specific to the BIOMARGIN study (discovery cohort, N=86; selection cohort, N=99; validation cohort, N=298), six differentially expressed miRNAs were consistently identified: miR-139-5p (down) and miR-142-3p/150-5p/155-5p/222-3p/223-3p (up). Their expression level gradually correlated with microvascular inflammation intensity. The cell specificity of miRNAs target genes was investigated by integrating their in vivo mRNA targets with single-cell RNA sequencing from an independent allograft biopsy cohort. Endothelial-derived miR-139-5p expression correlated negatively with MHC-related genes expression. Conversely, epithelial-derived miR-222-3p overexpression was strongly associated with degraded renal electrolyte homeostasis and repressed immune-related pathways. In immune cells, miR-150-5p regulated NF-κB activation in T lymphocytes whereas miR-155-5p regulated mRNA splicing in antigen-presenting cells. Altogether, integrated omics enabled us to unravel new pathways involved in microvascular inflammation and suggests that metabolism modifications in tubular epithelial cells occur as a consequence of antibody-mediated rejection, beyond the nearby endothelial compartment.
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spelling pubmed-85932472021-11-17 Integrative Omics Analysis Unravels Microvascular Inflammation-Related Pathways in Kidney Allograft Biopsies Tinel, Claire Lamarthée, Baptiste Callemeyn, Jasper Van Loon, Elisabet Sauvaget, Virginia Morin, Lise Aouni, Laïla Rabant, Marion Gwinner, Wilfried Marquet, Pierre Naesens, Maarten Anglicheau, Dany Front Immunol Immunology In solid-organ transplantation, microRNAs (miRNAs) have emerged as key players in the regulation of allograft cells function in response to injury. To gain insight into the role of miRNAs in antibody-mediated rejection, a rejection phenotype histologically defined by microvascular inflammation, kidney allograft biopsies were subjected to miRNA but also messenger RNA (mRNA) profiling. Using a unique multistep selection process specific to the BIOMARGIN study (discovery cohort, N=86; selection cohort, N=99; validation cohort, N=298), six differentially expressed miRNAs were consistently identified: miR-139-5p (down) and miR-142-3p/150-5p/155-5p/222-3p/223-3p (up). Their expression level gradually correlated with microvascular inflammation intensity. The cell specificity of miRNAs target genes was investigated by integrating their in vivo mRNA targets with single-cell RNA sequencing from an independent allograft biopsy cohort. Endothelial-derived miR-139-5p expression correlated negatively with MHC-related genes expression. Conversely, epithelial-derived miR-222-3p overexpression was strongly associated with degraded renal electrolyte homeostasis and repressed immune-related pathways. In immune cells, miR-150-5p regulated NF-κB activation in T lymphocytes whereas miR-155-5p regulated mRNA splicing in antigen-presenting cells. Altogether, integrated omics enabled us to unravel new pathways involved in microvascular inflammation and suggests that metabolism modifications in tubular epithelial cells occur as a consequence of antibody-mediated rejection, beyond the nearby endothelial compartment. Frontiers Media S.A. 2021-11-02 /pmc/articles/PMC8593247/ /pubmed/34795664 http://dx.doi.org/10.3389/fimmu.2021.738795 Text en Copyright © 2021 Tinel, Lamarthée, Callemeyn, Van Loon, Sauvaget, Morin, Aouni, Rabant, Gwinner, Marquet, Naesens and Anglicheau https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Tinel, Claire
Lamarthée, Baptiste
Callemeyn, Jasper
Van Loon, Elisabet
Sauvaget, Virginia
Morin, Lise
Aouni, Laïla
Rabant, Marion
Gwinner, Wilfried
Marquet, Pierre
Naesens, Maarten
Anglicheau, Dany
Integrative Omics Analysis Unravels Microvascular Inflammation-Related Pathways in Kidney Allograft Biopsies
title Integrative Omics Analysis Unravels Microvascular Inflammation-Related Pathways in Kidney Allograft Biopsies
title_full Integrative Omics Analysis Unravels Microvascular Inflammation-Related Pathways in Kidney Allograft Biopsies
title_fullStr Integrative Omics Analysis Unravels Microvascular Inflammation-Related Pathways in Kidney Allograft Biopsies
title_full_unstemmed Integrative Omics Analysis Unravels Microvascular Inflammation-Related Pathways in Kidney Allograft Biopsies
title_short Integrative Omics Analysis Unravels Microvascular Inflammation-Related Pathways in Kidney Allograft Biopsies
title_sort integrative omics analysis unravels microvascular inflammation-related pathways in kidney allograft biopsies
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8593247/
https://www.ncbi.nlm.nih.gov/pubmed/34795664
http://dx.doi.org/10.3389/fimmu.2021.738795
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