Autor: |
David J. Dittmar, Franziska Pielmeier, Nicholas Strieder, Alexander Fischer, Michael Herbst, Hanna Stanewsky, Niklas Wenzl, Eveline Röseler, Rüdiger Eder, Claudia Gebhard, Lucia Schwarzfischer-Pfeilschifter, Christin Albrecht, Wolfgang Herr, Matthias Edinger, Petra Hoffmann, Michael Rehli |
Jazyk: |
angličtina |
Rok vydání: |
2024 |
Předmět: |
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Zdroj: |
Nature Communications, Vol 15, Iss 1, Pp 1-16 (2024) |
Druh dokumentu: |
article |
ISSN: |
2041-1723 |
DOI: |
10.1038/s41467-024-47575-z |
Popis: |
Abstract The adoptive transfer of regulatory T cells is a promising strategy to prevent graft-versus-host disease after allogeneic bone marrow transplantation. Here, we use a major histocompatibility complex-mismatched mouse model to follow the fate of in vitro expanded donor regulatory T cells upon migration to target organs. Employing comprehensive gene expression and repertoire profiling, we show that they retain their suppressive function and plasticity after transfer. Upon entering non-lymphoid tissues, donor regulatory T cells acquire organ-specific gene expression profiles resembling tissue-resident cells and activate hallmark suppressive and cytotoxic pathways, most evidently in the colon, when co-transplanted with graft-versus-host disease-inducing conventional T cells. Dominant T cell receptor clonotypes overlap between organs and across recipients and their relative abundance correlates with protection efficacy. Thus, this study reveals donor regulatory T cell selection and adaptation mechanisms in target organs and highlights protective features of Treg to guide the development of improved graft-versus-host disease prevention strategies. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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