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Multimodal immune cell phenotyping in gastrointestinal biopsies reveals microbiome-related T cell modulations in human GvHD patients

GSE234357 Homo sapiens Expression profiling by high throughput sequencing; Other 18 samples Submitted 2023/06/18 Platform GPL24676
Summary
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 patients with fecal microbiome analysis, we could link high microbiome diversity and the abundance of short-chain fatty acid-producing bacteria to the sustenance of suppressive regulatory T cells. Furthermore, aGvHD severity was strongly associated with the clonal expansion of mainly CD8 T cells, which we found 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 towards more severe clinical manifestations and strongly supports the further development of microbiome interventions as GvHD treatment via repopulation of the gut Treg niche to suppress inflammation.
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Direct links to NCBI, no account and no request form: the whole study as GSE234357_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 18 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA981126 and SRA study SRP441726. Searching any of these in the dataset finder brings you back here.

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