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

• DOI: 10.1016/j.xcrm.2023.101125
• Publication Date: 2023-07-18T15:11:46Z
• Authors: 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
• Keywords: LGR5

Acute graft-versus-host disease (aGvHD) is a significant complication after allogeneic hematopoietic stem cell transplantation (aHSCT), but major factors determining 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 diversity the abundance of short-chain fatty acid-producing bacteria to sustenance suppressive regulatory T cells (Tregs). Furthermore, aGvHD strongly associates clonal expansion mainly CD8 cells, which find distributed over anatomically distant regions gut, persistent time, inversely correlated presence Tregs. Overall, our study highlights pathophysiological importance expanded clones in progression toward more severe clinical manifestations supports further development interventions as GvHD treatment via repopulation gut Treg niche suppress inflammation.