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Injured epithelial cell states impact kidney allograft survival after T-cell-mediated rejection

T-cell-mediated rejection (TCMR) remains a major cause of kidney transplant failure, despite being considered treatable. Its impact reflects a limited understanding of the underlying molecular mechanisms and their clinical consequences. To address this, we induced acute TCMR in mouse kidney transpla...

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Main Authors: Pfefferkorn, Anna Maria (Author) , Jahn, Lorenz (Author) , Gauthier, Patrick T. (Author) , Kulow, Vera Anna (Author) , Roeles, Johannes (Author) , Müller-Bötticher, Niklas (Author) , Gerhardt, Louisa M. S. (Author) , Leiz, Janna (Author) , Sarfraz, Sadia (Author) , Plumbom, Izabela (Author) , Greite, Robert (Author) , Lovric, Svjetlana (Author) , Gamrekelashvili, Jaba (Author) , Limbourg, Florian (Author) , Schmitz, Jessica (Author) , Bräsen, Jan Hinrich (Author) , Scheffner, Irina (Author) , Sauer, Igor M. (Author) , Aigner, Felix (Author) , Altmüller, Janine (Author) , Conrad, Thomas (Author) , Gwinner, Wilfried (Author) , Ishaque, Naveed (Author) , Fähling, Michael (Author) , Schmidt-Ott, Kai M. (Author) , Halloran, Philip F. (Author) , Ashraf, Muhammad Imtiaz (Author) , Hinze, Christian (Author)
Format: Article (Journal)
Language:English
Published: 28 January 2026
In: Nature Communications
Year: 2026, Volume: 17, Pages: 1-19
ISSN:2041-1723
DOI:10.1038/s41467-026-68397-1
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41467-026-68397-1
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41467-026-68397-1
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Author Notes:Anna Maria Pfefferkorn, Lorenz Jahn, Patrick T. Gauthier, Vera Anna Kulow, Johannes Roeles, Niklas Müller-Bötticher, Louisa M.S. Gerhardt, Janna Leiz, Sadia Sarfraz, Izabela Plumbom, Robert Greite, Svjetlana Lovric, Jaba Gamrekelashvili, Florian Limbourg, Jessica Schmitz, Jan Hinrich Bräsen, Irina Scheffner, Igor M. Sauer, Felix Aigner, Janine Altmüller, Thomas Conrad, Wilfried Gwinner, Naveed Ishaque, Michael Fähling, Kai M. Schmidt-Ott, Philip F. Halloran, Muhammad Imtiaz Ashraf & Christian Hinze
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Summary:T-cell-mediated rejection (TCMR) remains a major cause of kidney transplant failure, despite being considered treatable. Its impact reflects a limited understanding of the underlying molecular mechanisms and their clinical consequences. To address this, we induced acute TCMR in mouse kidney transplants and profiled molecular changes using single-nucleus RNA sequencing (snRNA-seq), spatial transcriptomics and immunofluorescence. Results were compared with human snRNA-seq data from TCMR and stable allografts, as well as single-cell deconvolution analysis of bulk transcriptomic data from kidney transplant biopsies. Here we show that TCMR induces injured epithelial cell states in mouse kidney allografts, particularly in proximal tubules and thick ascending limbs. Spatial transcriptomics of these injured epithelial states demonstrated heterogeneous localization, interactions with immune cells and cellular microenvironments. Cross-species analysis confirmed similar severely injured epithelial states in human samples, whose abundances correlated with transplant survival and persisted despite TCMR resolution. Collectively, our results identify epithelial injury cell states as a determinant of outcome after TCMR.
Item Description:Gesehen am 28.04.2026
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-026-68397-1

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