Abstract: TH-PO0889
Epithelial Injury Cell States Affect Kidney Transplant Survival After T Cell-Mediated Rejection
Session Information
- Transplantation: Basic Research
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2101 Transplantation: Basic
Authors
- Jahn, Lorenz, Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany
- Pfefferkorn, Anna Maria, Department of Surgery, Experimental Surgery, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
- Gauthier, Patrick T, Alberta Transplant Applied Genomics Centre, Edmonton, Alberta, Canada
- Kulow, Vera Anna, Institute of Translational Physiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Leiz, Janna, Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany
- Lovric, Svjetlana, Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany
- Schmitz, Jessica, Nephropathology Unit, Institute of Pathology, Hannover Medical School, Hannover, Germany
- Scheffner, Irina, Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany
- Roeles, Johannes, Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany
- Greite, Robert, Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany
- Fähling, Michael, Institute of Translational Physiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- Sauer, Igor M., Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany
- Aigner, Felix, Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany
- Altmüller, Janine, Genomics Technology Platform, Max Delbrück Center for Molecular Medicine, Berlin, Germany
- Conrad, Thomas, Genomics Technology Platform, Max Delbrück Center for Molecular Medicine, Berlin, Germany
- Gwinner, Wilfried, Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany
- Ishaque, Naveed, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Center of Digital Health, Berlin, Germany
- Schmidt-Ott, Kai M., Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany
- Halloran, Philip F., Alberta Transplant Applied Genomics Centre, Edmonton, Alberta, Canada
- Ashraf, Muhammad Imtiaz, Department of Surgery, Experimental Surgery, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany
- Hinze, Christian, Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany
Background
T-cell-mediated rejection (TCMR) remains a key obstacle to achieving long-term survival of kidney allografts. Although it is generally considered responsive to intensified immunosuppression, its occurrence still significantly impairs graft function and durability. This is largely due to an incomplete understanding of the molecular pathways activated during TCMR and their clinical implications.
Methods
To investigate this, we induced acute TCMR in murine models of allogeneic kidney transplantation (C57BL/6 to BALB/c and BALB/c to C57BL/6), alongside syngeneic controls (C57BL/6 to C57BL/6 and BALB/c to BALB/c). Molecular alterations were examined 7 days post-transplant using single-nucleus RNA sequencing (snRNA-seq) and spatial transcriptomics. Findings were compared with snRNA-seq data from three human TCMR biopsies and three stable allografts without rejection. To assess clinical relevance, we analyzed bulk transcriptomic data from 1,292 kidney allografts—including 95 TCMR cases—using biomarker gene sets reflecting TCMR-associated epithelial injury and allograft outcomes.
Results
Allogeneic mouse kidneys showed classical histopathological signs of TCMR. snRNA-seq revealed distinct injury-associated cell states with marked gene expression changes, especially in proximal tubules (PT) and thick ascending limbs (TAL). Spatial transcriptomics identified a heterogeneous distribution of these injured cells and their spatial association with infiltrating leukocytes. Cross-species comparison demonstrated conserved injured PT and TAL cell states in human TCMR. Importantly, graft outcomes were closely linked to the extent of TCMR-induced epithelial injury, which persisted in some cases despite apparent resolution of rejection.
Conclusion
This study provides an in-depth analysis of cell type-specific molecular changes during TCMR across species. The findings underscore the need for improved diagnostic tools and targeted therapies to address epithelial injury and enhance long-term kidney allograft survival.