Impact of wild-type intestinal microbiome on impaired immune regulation during acute graft-versus-host disease (B10*)

• Subject Area: Hematology, Oncology ; Rheumatology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 256073931

In the project, Rosshart/Zeiser plan to decipher the impact of a wildling microbiome on intestinal damage during GvHD. They will test the hypothesis that a wildling microbiome leads to more aggressive acute GvHD (aGvHD) based on increased activation of T cells and neutrophils. They will also assess the impact of a wildling microbiome on intestinal repair mechanisms and GVL effects. Based on previous work showing that glucagon like peptide-2 (GLP2) mediated tissue repair reduces aGvHD severity, the impact of GLP2 treatment on GvHD will be tested in wildling mice to better reflect the situation in patients. We will also compare the wildling versus specific-pathogen-free (SPF) microbiome-derived metabolites to identify targets for prevention of immune dysregulation during aGvHD and validate these findings in samples derived from GvHD patients.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1160: Immune-mediated pathology as a consequence of impaired immune reactions (IMPATH)
• Applicant Institution: Albert-Ludwigs-Universität Freiburg
• Project Heads: Professor Dr. Stephan Patrick Rosshart; Professor Dr. Robert Zeiser