Jarosch, Sebastian and Koehlen, Jan and Ghimire, Sakhila and Orberg, Erik Thiele and Hammel, Monika and Gaag, Doris and Evert, Matthias and Janssen, Klaus-Peter and Hiergeist, Andreas and Gessner, Andre and Weber, Daniela and Meedt, Elisabeth and Poeck, Hendrik and D'Ippolito, Elvira and Holler, Ernst and Busch, Dirk H. (2023) Multimodal immune cell phenotyping in GI biopsies reveals microbiome-related T cell modulations in human GvHD. CELL REPORTS MEDICINE, 4 (7): 101125. ISSN 2666-3791,
Full text not available from this repository. (Request a copy)Abstract
Acute graft-versus-host disease (aGvHD) is a significant complication after allogeneic hematopoietic stem cell transplantation (aHSCT), but major factors determining disease severity are not well defined yet. By combining multiplexed tissue imaging and single-cell RNA sequencing on gastrointestinal biopsies from aHSCT-treated individuals with fecal microbiome analysis, we link high microbiome diversity and the abun-dance of short-chain fatty acid-producing bacteria to the sustenance of suppressive regulatory T cells (Tregs). Furthermore, aGvHD severity strongly associates with the clonal expansion of mainly CD8 T cells, which we find distributed over anatomically distant regions of the gut, persistent over time, and inversely correlated with the presence of suppressive Tregs. Overall, our study highlights the pathophysiological importance of expanded CD8 T cell clones in the progression of aGvHD toward more severe clinical manifes-tations and strongly supports the further development of microbiome interventions as GvHD treatment via repopulation of the gut Treg niche to suppress inflammation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | VERSUS-HOST-DISEASE; STEM-CELL; FECAL MICROBIOTA; BONE-MARROW; TRANSCRIPTION FACTOR; HUMAN RECIPIENTS; TRANSPLANTATION; RECONSTITUTION; DIVERSITY; RECEPTOR; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Jan 2024 09:52 |
| Last Modified: | 30 Jan 2024 09:52 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60068 |
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