Cargando…

Transcriptional and spatial profiling of the kidney allograft unravels a central role for FcyRIII+ innate immune cells in rejection

Rejection remains the main cause of premature graft loss after kidney transplantation, despite the use of potent immunosuppression. This highlights the need to better understand the composition and the cell-to-cell interactions of the alloreactive inflammatory infiltrate. Here, we performed droplet-...

Descripción completa

Detalles Bibliográficos
Autores principales: Lamarthée, Baptiste, Callemeyn, Jasper, Van Herck, Yannick, Antoranz, Asier, Anglicheau, Dany, Boada, Patrick, Becker, Jan Ulrich, Debyser, Tim, De Smet, Frederik, De Vusser, Katrien, Eloudzeri, Maëva, Franken, Amelie, Gwinner, Wilfried, Koshy, Priyanka, Kuypers, Dirk, Lambrechts, Diether, Marquet, Pierre, Mathias, Virginie, Rabant, Marion, Sarwal, Minnie M., Senev, Aleksandar, Sigdel, Tara K., Sprangers, Ben, Thaunat, Olivier, Tinel, Claire, Van Brussel, Thomas, Van Craenenbroeck, Amaryllis, Van Loon, Elisabet, Vaulet, Thibaut, Bosisio, Francesca, Naesens, Maarten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10356785/
https://www.ncbi.nlm.nih.gov/pubmed/37468466
http://dx.doi.org/10.1038/s41467-023-39859-7
_version_ 1785075350640787456
author Lamarthée, Baptiste
Callemeyn, Jasper
Van Herck, Yannick
Antoranz, Asier
Anglicheau, Dany
Boada, Patrick
Becker, Jan Ulrich
Debyser, Tim
De Smet, Frederik
De Vusser, Katrien
Eloudzeri, Maëva
Franken, Amelie
Gwinner, Wilfried
Koshy, Priyanka
Kuypers, Dirk
Lambrechts, Diether
Marquet, Pierre
Mathias, Virginie
Rabant, Marion
Sarwal, Minnie M.
Senev, Aleksandar
Sigdel, Tara K.
Sprangers, Ben
Thaunat, Olivier
Tinel, Claire
Van Brussel, Thomas
Van Craenenbroeck, Amaryllis
Van Loon, Elisabet
Vaulet, Thibaut
Bosisio, Francesca
Naesens, Maarten
author_facet Lamarthée, Baptiste
Callemeyn, Jasper
Van Herck, Yannick
Antoranz, Asier
Anglicheau, Dany
Boada, Patrick
Becker, Jan Ulrich
Debyser, Tim
De Smet, Frederik
De Vusser, Katrien
Eloudzeri, Maëva
Franken, Amelie
Gwinner, Wilfried
Koshy, Priyanka
Kuypers, Dirk
Lambrechts, Diether
Marquet, Pierre
Mathias, Virginie
Rabant, Marion
Sarwal, Minnie M.
Senev, Aleksandar
Sigdel, Tara K.
Sprangers, Ben
Thaunat, Olivier
Tinel, Claire
Van Brussel, Thomas
Van Craenenbroeck, Amaryllis
Van Loon, Elisabet
Vaulet, Thibaut
Bosisio, Francesca
Naesens, Maarten
author_sort Lamarthée, Baptiste
collection PubMed
description Rejection remains the main cause of premature graft loss after kidney transplantation, despite the use of potent immunosuppression. This highlights the need to better understand the composition and the cell-to-cell interactions of the alloreactive inflammatory infiltrate. Here, we performed droplet-based single-cell RNA sequencing of 35,152 transcriptomes from 16 kidney transplant biopsies with varying phenotypes and severities of rejection and without rejection, and identified cell-type specific gene expression signatures for deconvolution of bulk tissue. A specific association was identified between recipient-derived FCGR3A+ monocytes, FCGR3A+ NK cells and the severity of intragraft inflammation. Activated FCGR3A+ monocytes overexpressed CD47 and LILR genes and increased paracrine signaling pathways promoting T cell infiltration. FCGR3A+ NK cells overexpressed FCRL3, suggesting that antibody-dependent cytotoxicity is a central mechanism of NK-cell mediated graft injury. Multiplexed immunofluorescence using 38 markers on 18 independent biopsy slides confirmed this role of FcγRIII+ NK and FcγRIII+ nonclassical monocytes in antibody-mediated rejection, with specificity to the glomerular area. These results highlight the central involvement of innate immune cells in the pathogenesis of allograft rejection and identify several potential therapeutic targets that might improve allograft longevity.
format Online
Article
Text
id pubmed-10356785
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-103567852023-07-21 Transcriptional and spatial profiling of the kidney allograft unravels a central role for FcyRIII+ innate immune cells in rejection Lamarthée, Baptiste Callemeyn, Jasper Van Herck, Yannick Antoranz, Asier Anglicheau, Dany Boada, Patrick Becker, Jan Ulrich Debyser, Tim De Smet, Frederik De Vusser, Katrien Eloudzeri, Maëva Franken, Amelie Gwinner, Wilfried Koshy, Priyanka Kuypers, Dirk Lambrechts, Diether Marquet, Pierre Mathias, Virginie Rabant, Marion Sarwal, Minnie M. Senev, Aleksandar Sigdel, Tara K. Sprangers, Ben Thaunat, Olivier Tinel, Claire Van Brussel, Thomas Van Craenenbroeck, Amaryllis Van Loon, Elisabet Vaulet, Thibaut Bosisio, Francesca Naesens, Maarten Nat Commun Article Rejection remains the main cause of premature graft loss after kidney transplantation, despite the use of potent immunosuppression. This highlights the need to better understand the composition and the cell-to-cell interactions of the alloreactive inflammatory infiltrate. Here, we performed droplet-based single-cell RNA sequencing of 35,152 transcriptomes from 16 kidney transplant biopsies with varying phenotypes and severities of rejection and without rejection, and identified cell-type specific gene expression signatures for deconvolution of bulk tissue. A specific association was identified between recipient-derived FCGR3A+ monocytes, FCGR3A+ NK cells and the severity of intragraft inflammation. Activated FCGR3A+ monocytes overexpressed CD47 and LILR genes and increased paracrine signaling pathways promoting T cell infiltration. FCGR3A+ NK cells overexpressed FCRL3, suggesting that antibody-dependent cytotoxicity is a central mechanism of NK-cell mediated graft injury. Multiplexed immunofluorescence using 38 markers on 18 independent biopsy slides confirmed this role of FcγRIII+ NK and FcγRIII+ nonclassical monocytes in antibody-mediated rejection, with specificity to the glomerular area. These results highlight the central involvement of innate immune cells in the pathogenesis of allograft rejection and identify several potential therapeutic targets that might improve allograft longevity. Nature Publishing Group UK 2023-07-19 /pmc/articles/PMC10356785/ /pubmed/37468466 http://dx.doi.org/10.1038/s41467-023-39859-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Lamarthée, Baptiste
Callemeyn, Jasper
Van Herck, Yannick
Antoranz, Asier
Anglicheau, Dany
Boada, Patrick
Becker, Jan Ulrich
Debyser, Tim
De Smet, Frederik
De Vusser, Katrien
Eloudzeri, Maëva
Franken, Amelie
Gwinner, Wilfried
Koshy, Priyanka
Kuypers, Dirk
Lambrechts, Diether
Marquet, Pierre
Mathias, Virginie
Rabant, Marion
Sarwal, Minnie M.
Senev, Aleksandar
Sigdel, Tara K.
Sprangers, Ben
Thaunat, Olivier
Tinel, Claire
Van Brussel, Thomas
Van Craenenbroeck, Amaryllis
Van Loon, Elisabet
Vaulet, Thibaut
Bosisio, Francesca
Naesens, Maarten
Transcriptional and spatial profiling of the kidney allograft unravels a central role for FcyRIII+ innate immune cells in rejection
title Transcriptional and spatial profiling of the kidney allograft unravels a central role for FcyRIII+ innate immune cells in rejection
title_full Transcriptional and spatial profiling of the kidney allograft unravels a central role for FcyRIII+ innate immune cells in rejection
title_fullStr Transcriptional and spatial profiling of the kidney allograft unravels a central role for FcyRIII+ innate immune cells in rejection
title_full_unstemmed Transcriptional and spatial profiling of the kidney allograft unravels a central role for FcyRIII+ innate immune cells in rejection
title_short Transcriptional and spatial profiling of the kidney allograft unravels a central role for FcyRIII+ innate immune cells in rejection
title_sort transcriptional and spatial profiling of the kidney allograft unravels a central role for fcyriii+ innate immune cells in rejection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10356785/
https://www.ncbi.nlm.nih.gov/pubmed/37468466
http://dx.doi.org/10.1038/s41467-023-39859-7
work_keys_str_mv AT lamartheebaptiste transcriptionalandspatialprofilingofthekidneyallograftunravelsacentralroleforfcyriiiinnateimmunecellsinrejection
AT callemeynjasper transcriptionalandspatialprofilingofthekidneyallograftunravelsacentralroleforfcyriiiinnateimmunecellsinrejection
AT vanherckyannick transcriptionalandspatialprofilingofthekidneyallograftunravelsacentralroleforfcyriiiinnateimmunecellsinrejection
AT antoranzasier transcriptionalandspatialprofilingofthekidneyallograftunravelsacentralroleforfcyriiiinnateimmunecellsinrejection
AT anglicheaudany transcriptionalandspatialprofilingofthekidneyallograftunravelsacentralroleforfcyriiiinnateimmunecellsinrejection
AT boadapatrick transcriptionalandspatialprofilingofthekidneyallograftunravelsacentralroleforfcyriiiinnateimmunecellsinrejection
AT beckerjanulrich transcriptionalandspatialprofilingofthekidneyallograftunravelsacentralroleforfcyriiiinnateimmunecellsinrejection
AT debysertim transcriptionalandspatialprofilingofthekidneyallograftunravelsacentralroleforfcyriiiinnateimmunecellsinrejection
AT desmetfrederik transcriptionalandspatialprofilingofthekidneyallograftunravelsacentralroleforfcyriiiinnateimmunecellsinrejection
AT devusserkatrien transcriptionalandspatialprofilingofthekidneyallograftunravelsacentralroleforfcyriiiinnateimmunecellsinrejection
AT eloudzerimaeva transcriptionalandspatialprofilingofthekidneyallograftunravelsacentralroleforfcyriiiinnateimmunecellsinrejection
AT frankenamelie transcriptionalandspatialprofilingofthekidneyallograftunravelsacentralroleforfcyriiiinnateimmunecellsinrejection
AT gwinnerwilfried transcriptionalandspatialprofilingofthekidneyallograftunravelsacentralroleforfcyriiiinnateimmunecellsinrejection
AT koshypriyanka transcriptionalandspatialprofilingofthekidneyallograftunravelsacentralroleforfcyriiiinnateimmunecellsinrejection
AT kuypersdirk transcriptionalandspatialprofilingofthekidneyallograftunravelsacentralroleforfcyriiiinnateimmunecellsinrejection
AT lambrechtsdiether transcriptionalandspatialprofilingofthekidneyallograftunravelsacentralroleforfcyriiiinnateimmunecellsinrejection
AT marquetpierre transcriptionalandspatialprofilingofthekidneyallograftunravelsacentralroleforfcyriiiinnateimmunecellsinrejection
AT mathiasvirginie transcriptionalandspatialprofilingofthekidneyallograftunravelsacentralroleforfcyriiiinnateimmunecellsinrejection
AT rabantmarion transcriptionalandspatialprofilingofthekidneyallograftunravelsacentralroleforfcyriiiinnateimmunecellsinrejection
AT sarwalminniem transcriptionalandspatialprofilingofthekidneyallograftunravelsacentralroleforfcyriiiinnateimmunecellsinrejection
AT senevaleksandar transcriptionalandspatialprofilingofthekidneyallograftunravelsacentralroleforfcyriiiinnateimmunecellsinrejection
AT sigdeltarak transcriptionalandspatialprofilingofthekidneyallograftunravelsacentralroleforfcyriiiinnateimmunecellsinrejection
AT sprangersben transcriptionalandspatialprofilingofthekidneyallograftunravelsacentralroleforfcyriiiinnateimmunecellsinrejection
AT thaunatolivier transcriptionalandspatialprofilingofthekidneyallograftunravelsacentralroleforfcyriiiinnateimmunecellsinrejection
AT tinelclaire transcriptionalandspatialprofilingofthekidneyallograftunravelsacentralroleforfcyriiiinnateimmunecellsinrejection
AT vanbrusselthomas transcriptionalandspatialprofilingofthekidneyallograftunravelsacentralroleforfcyriiiinnateimmunecellsinrejection
AT vancraenenbroeckamaryllis transcriptionalandspatialprofilingofthekidneyallograftunravelsacentralroleforfcyriiiinnateimmunecellsinrejection
AT vanloonelisabet transcriptionalandspatialprofilingofthekidneyallograftunravelsacentralroleforfcyriiiinnateimmunecellsinrejection
AT vauletthibaut transcriptionalandspatialprofilingofthekidneyallograftunravelsacentralroleforfcyriiiinnateimmunecellsinrejection
AT bosisiofrancesca transcriptionalandspatialprofilingofthekidneyallograftunravelsacentralroleforfcyriiiinnateimmunecellsinrejection
AT naesensmaarten transcriptionalandspatialprofilingofthekidneyallograftunravelsacentralroleforfcyriiiinnateimmunecellsinrejection