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

Autor: Lamarthée B; Department of Microbiology, Immunology and Transplantation, Nephrology and Kidney Transplantation Research Group, KU Leuven, Leuven, Belgium.; Université de Franche-Comté, UBFC, EFS, Inserm UMR RIGHT, Besançon, France., Callemeyn J; Department of Microbiology, Immunology and Transplantation, Nephrology and Kidney Transplantation Research Group, KU Leuven, Leuven, Belgium.; Department of Nephrology and Kidney Transplantation, University Hospitals Leuven, Leuven, Belgium., Van Herck Y; Department of Oncology, Laboratory for Experimental Oncology, KU Leuven, Leuven, Belgium., Antoranz A; Department of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven, Leuven, Belgium., Anglicheau D; Department of Nephrology and Kidney Transplantation, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.; Université Paris Cité, Inserm U1151, Necker Enfants-Malades Institute, Paris, France., Boada P; Division of Multi-Organ Transplantation, Department of Surgery, UCSF, 513 Parnassus, San Francisco, CA, USA., Becker JU; Institute of Pathology, University Hospital Cologne, Cologne, Germany., Debyser T; Department of Microbiology, Immunology and Transplantation, Nephrology and Kidney Transplantation Research Group, KU Leuven, Leuven, Belgium., De Smet F; Department of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven, Leuven, Belgium., De Vusser K; Department of Microbiology, Immunology and Transplantation, Nephrology and Kidney Transplantation Research Group, KU Leuven, Leuven, Belgium.; Department of Nephrology and Kidney Transplantation, University Hospitals Leuven, Leuven, Belgium., Eloudzeri M; Université Paris Cité, Inserm U1151, Necker Enfants-Malades Institute, Paris, France., Franken A; VIB Center for Cancer Biology, Leuven, Belgium.; Department of Human Genetics, Laboratory of Translational Genetics, KU Leuven, Leuven, Belgium., Gwinner W; Department of Nephrology, Hannover Medical School, Hannover, Germany., Koshy P; Department of Imaging and Pathology, KU Leuven, Leuven, Belgium., Kuypers D; Department of Microbiology, Immunology and Transplantation, Nephrology and Kidney Transplantation Research Group, KU Leuven, Leuven, Belgium.; Department of Nephrology and Kidney Transplantation, University Hospitals Leuven, Leuven, Belgium., Lambrechts D; VIB Center for Cancer Biology, Leuven, Belgium.; Department of Human Genetics, Laboratory of Translational Genetics, KU Leuven, Leuven, Belgium., Marquet P; Department of Pharmacology and Transplantation, University of Limoges, Inserm U1248, Limoges University Hospital, Limoges, France., Mathias V; EFS, HLA Laboratory, Décines, France.; Université Claude Bernard Lyon I, Inserm U1111, CNRS UMR5308, CIRI, Ecole Normale Supérieure de Lyon, Lyon, France., Rabant M; Université Paris Cité, Inserm U1151, Necker Enfants-Malades Institute, Paris, France.; Department of Pathology, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France., Sarwal MM; Division of Multi-Organ Transplantation, Department of Surgery, UCSF, 513 Parnassus, San Francisco, CA, USA., Senev A; Department of Microbiology, Immunology and Transplantation, Nephrology and Kidney Transplantation Research Group, KU Leuven, Leuven, Belgium.; Histocompatibility and Immunogenetics Laboratory, Red Cross-Flanders, Mechelen, Belgium., Sigdel TK; Division of Multi-Organ Transplantation, Department of Surgery, UCSF, 513 Parnassus, San Francisco, CA, USA., Sprangers B; Department of Microbiology, Immunology and Transplantation, Nephrology and Kidney Transplantation Research Group, KU Leuven, Leuven, Belgium.; Department of Nephrology and Kidney Transplantation, University Hospitals Leuven, Leuven, Belgium., Thaunat O; Université Claude Bernard Lyon I, Inserm U1111, CNRS UMR5308, CIRI, Ecole Normale Supérieure de Lyon, Lyon, France.; Hospices Civils de Lyon, Edouard Herriot Hospital, Department of Transplantation, Nephrology and Clinical Immunology, Lyon, France., Tinel C; Department of Microbiology, Immunology and Transplantation, Nephrology and Kidney Transplantation Research Group, KU Leuven, Leuven, Belgium.; Université de Franche-Comté, UBFC, EFS, Inserm UMR RIGHT, Besançon, France.; Department of Nephrology and Kidney Transplantation, Dijon Hospital, Dijon, France., Van Brussel T; VIB Center for Cancer Biology, Leuven, Belgium.; Department of Human Genetics, Laboratory of Translational Genetics, KU Leuven, Leuven, Belgium., Van Craenenbroeck A; Department of Microbiology, Immunology and Transplantation, Nephrology and Kidney Transplantation Research Group, KU Leuven, Leuven, Belgium.; Department of Nephrology and Kidney Transplantation, University Hospitals Leuven, Leuven, Belgium., Van Loon E; Department of Microbiology, Immunology and Transplantation, Nephrology and Kidney Transplantation Research Group, KU Leuven, Leuven, Belgium.; Department of Nephrology and Kidney Transplantation, University Hospitals Leuven, Leuven, Belgium., Vaulet T; Department of Microbiology, Immunology and Transplantation, Nephrology and Kidney Transplantation Research Group, KU Leuven, Leuven, Belgium., Bosisio F; Department of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven, Leuven, Belgium., Naesens M; Department of Microbiology, Immunology and Transplantation, Nephrology and Kidney Transplantation Research Group, KU Leuven, Leuven, Belgium. maarten.naesens@uzleuven.be.; Department of Nephrology and Kidney Transplantation, University Hospitals Leuven, Leuven, Belgium. maarten.naesens@uzleuven.be.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Jul 19; Vol. 14 (1), pp. 4359. Date of Electronic Publication: 2023 Jul 19.
DOI: 10.1038/s41467-023-39859-7
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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