Donor-But Not Recipient-Derived Cells Produce Collagen-1 in Chronically Rejected Cardiac Allografts

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,

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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
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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