Balam, Saidou and Buchtler, Simone and Winter, Frederike and Schmidbauer, Kathrin and Neumayer, Sophia and Talke, Yvonne and Renner, Kerstin and Geissler, Edward K. and Mack, Matthias (2022) Donor-But Not Recipient-Derived Cells Produce Collagen-1 in Chronically Rejected Cardiac Allografts. FRONTIERS IN IMMUNOLOGY, 12: 816509. ISSN 1664-3224,
Full text not available from this repository. (Request a copy)Abstract
Fibrosis is a prominent feature of chronic allograft rejection, caused by an excessive production of matrix proteins, including collagen-1. Several cell types produce collagen-1, including mesenchymal fibroblasts and cells of hematopoietic origin. Here, we sought to determine whether tissue-resident donor-derived cells or allograft-infiltrating recipient-derived cells are responsible for allograft fibrosis, and whether hematopoietic cells contribute to collagen production. A fully MHC-mismatched mouse heterotopic heart transplantation model was used, with transient depletion of CD4(+) T cells to prevent acute rejection. Collagen-1 was selectively knocked out in recipients or donors. In addition, collagen-1 was specifically deleted in hematopoietic cells. Tissue-resident macrophages were depleted using anti-CSF1R antibody. Allograft fibrosis and inflammation were quantified 20 days post-transplantation. Selective collagen-1 knock-out in recipients or donors showed that tissue-resident cells from donor hearts, but not infiltrating recipient-derived cells, are responsible for production of collagen-1 in allografts. Cell-type-specific knock-out experiments showed that hematopoietic tissue-resident cells in donor hearts substantially contributed to graft fibrosis. Tissue resident macrophages, however, were not responsible for collagen-production, as their deletion worsened allograft fibrosis. Donor-derived cells including those of hematopoietic origin determine allograft fibrosis, making them attractive targets for organ preconditioning to improve long-term transplantation outcomes.
Item Type: | Article |
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Uncontrolled Keywords: | MACROPHAGE ACTIVATION; T-CELLS; EXPRESSION; FIBROSIS; MYOFIBROBLASTS; CONTRIBUTE; CHEMOKINES; HEARTS; CSF-1; MICE; transplantation; fibrocytes; collagen-1; allograft fibrosis; chronic rejection |
Subjects: | 600 Technology > 610 Medical sciences Medicine |
Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Abteilung für Nephrologie Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
Depositing User: | Dr. Gernot Deinzer |
Date Deposited: | 17 Oct 2023 13:55 |
Last Modified: | 17 Oct 2023 13:55 |
URI: | https://pred.uni-regensburg.de/id/eprint/56443 |
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