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Glucagon-like peptide 2 for intestinal stem cell and Paneth cell repair during graft-versus-host disease in mice and humans by Johana Norona; Petya Apostolova; Dominik Schmidt; Rebekka Ihlemann; Nadine Reischmann; Gregory Taylor; Natalie Köhler; Jocelyn de Heer; Steffen Heeg; Geoffroy Andrieux; Benjamin A. Siranosian; Annette Schmitt-Graeff; Dietmar Pfeifer; Antonella Catalano; Ian J. Frew; Michele Proietti; Bodo Grimbacher; Alla Bulashevska; Ami S. Bhatt; Tilman Brummer; Till Clauditz; Tatjana Zabelina; Nicolaus Kroeger; Bruce R. Blazar; Melanie Boerries; Francis Ayuk; Robert Zeiser is a Medicine article available to read on EtoBox.

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## Abstract Acute graft-versus-host disease (GVHD) is a life-threatening complication after allogeneic hematopoietic cell transplantation (allo-HCT). Although currently used GVHD treatment regimens target the donor immune system, we explored here an approach that aims at protecting and regenerating Paneth cells (PCs) and intestinal stem cells (ISCs). Glucagon-like-peptide-2 (GLP-2) is an enteroendocrine tissue hormone produced by intestinal L cells. We observed that acute GVHD reduced intestinal GLP-2 levels in mice and patients developing GVHD. Treatment with the GLP-2 agonist, teduglutide, reduced de novo acute GVHD and steroid-refractory GVHD, without compromising graft-versus-leukemia (GVL) effects in multiple mouse models. Mechanistically GLP-2 substitution promoted regeneration of PCs and ISCs, which enhanced production of antimicrobial peptides and caused microbiome changes. GLP-2 expanded intestinal organoids and reduced expression of apoptosis-related genes. Low numbers of L cells in intestinal biopsies and high serum levels of GLP-2 were associated with a higher incidence of nonrelapse mortality in patients undergoing allo-HCT. Our findings indicate that L cells are a tar

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Author

Johana Norona; Petya Apostolova; Dominik Schmidt; Rebekka Ihlemann; Nadine Reischmann; Gregory Taylor; Natalie Köhler; Jocelyn de Heer; Steffen Heeg; Geoffroy Andrieux; Benjamin A. Siranosian; Annette Schmitt-Graeff; Dietmar Pfeifer; Antonella Catalano; Ian J. Frew; Michele Proietti; Bodo Grimbacher; Alla Bulashevska; Ami S. Bhatt; Tilman Brummer; Till Clauditz; Tatjana Zabelina; Nicolaus Kroeger; Bruce R. Blazar; Melanie Boerries; Francis Ayuk; Robert Zeiser

Publisher

American Society of Hematology

Published

2020

Language

EN

Field

Medicine (Health Sciences)