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Updated: Jan 30, 2026

Mouse Kidney Transplantation: Models of Allograft Rejection
16:15

Mouse Kidney Transplantation: Models of Allograft Rejection

Published on: October 11, 2014

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

Anna Maria Pfefferkorn1, Lorenz Jahn2, Patrick T Gauthier3

  • 1Department of Surgery, Experimental Surgery, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.

Nature Communications
|January 28, 2026
PubMed

Insights

Kidney transplant failure due to T-cell-mediated rejection (TCMR) is linked to specific injured epithelial cell states. These cell states in proximal tubules and thick ascending limbs impact transplant survival, even after rejection resolves.

Area of Science:

  • Nephrology
  • Immunology
  • Translational Medicine

Background:

  • T-cell-mediated rejection (TCMR) is a primary cause of kidney transplant failure.
  • Limited understanding of TCMR molecular mechanisms hinders effective treatment and outcomes.
  • Identifying molecular drivers of TCMR is crucial for improving graft survival.

Purpose of the Study:

  • To investigate the molecular and cellular changes associated with T-cell-mediated rejection in kidney allografts.
  • To identify specific cell states and their role in transplant outcomes.
  • To compare findings between mouse models and human kidney transplant biopsies.

Main Methods:

  • Induction of acute TCMR in mouse kidney allografts.
  • Single-nucleus RNA sequencing (snRNA-seq) and spatial transcriptomics.
  • Immunofluorescence, cross-species analysis with human data, and deconvolution of bulk transcriptomics.

Main Results:

  • TCMR induces distinct injured epithelial cell states in mouse kidney allografts, notably in proximal tubules and thick ascending limbs.
  • Spatial transcriptomics revealed heterogeneous localization and immune cell interactions within these injured epithelial states.
  • Similar injured epithelial cell states were identified in human TCMR allografts, correlating with transplant survival and persisting post-rejection.

Conclusions:

  • Epithelial injury cell states are a significant determinant of outcomes following T-cell-mediated rejection.
  • These findings highlight the critical role of epithelial health in kidney transplant success.
  • Targeting these specific epithelial cell states may offer novel therapeutic strategies for preventing transplant failure.

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