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

Project Summary

In Project B10(N), 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. B10(N) 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.