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

Baptiste Lamarthée, Jasper Callemeyn, Yannick Van Herck, Asier Antoranz, Dany Anglicheau, Patrick Boada, Jan Ulrich Becker, Tim Debyser, Frederik De Smet, Katrien De Vusser, Maëva Eloudzeri, Amelie Franken, Wilfried Gwinner, Priyanka Koshy, Dirk Kuypers, Diether Lambrechts, Pierre Marquet, Virginie Mathias, Marion Rabant, Minnie M. SarwalAleksandar Senev, Tara K. Sigdel, Ben Sprangers, Olivier Thaunat, Claire Tinel, Thomas Van Brussel, Amaryllis Van Craenenbroeck, Elisabet Van Loon, Thibaut Vaulet, Francesca Bosisio, Maarten Naesens*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number4359
JournalNature communications
Volume14
Issue number1
DOIs
StatePublished - Dec 2023

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

Fingerprint

Dive into the research topics of 'Transcriptional and spatial profiling of the kidney allograft unravels a central role for FcyRIII+ innate immune cells in rejection'. Together they form a unique fingerprint.

Cite this