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

Sebastian Jarosch, Jan Köhlen, Sakhila Ghimire, Erik Thiele Orberg, Monika Hammel, Doris Gaag, Matthias Evert, Klaus Peter Janssen, Andreas Hiergeist, André Gessner, Daniela Weber, Elisabeth Meedt, Hendrik Poeck, Elvira D'Ippolito, Ernst Holler, Dirk H. Busch

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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 abundance 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 manifestations and strongly supports the further development of microbiome interventions as GvHD treatment via repopulation of the gut Treg niche to suppress inflammation.

Original languageEnglish
Article number101125
JournalCell Reports Medicine
Volume4
Issue number7
DOIs
StatePublished - 18 Jul 2023
Externally publishedYes

Keywords

  • T cell infiltrate
  • allogeneic hematopoietic stem cell transplantation
  • chip cytometry
  • gastrointestinal biopsies
  • graft-versus-host disease
  • microbiome
  • multimodal immune cell phenotyping
  • multiplexed tissue imaging
  • single-cell RNA sequencing

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