Loss of L-cells due to acute graft-versus-host disease leads to Paneth cell defects which can be compensated by glucagon like peptide-2. Loss of L-cells due to acute graft-versus-host disease leads to Paneth cell defects which can be compensated by glucagon like peptide-2

Paneth cells are targets of allo-reactive T cells during acute graft-versus-host disease (GVHD). GVHD-related loss of Paneth cells is connected to intestinal dysbiosis and a decline of antimicrobial peptides. Glucagon-like-peptide-2 (GLP-2) is an enteroendocrine tissue hormone, produced by the intestinal L-cells, that leads to expansion of Paneth cells. Microarray-based analysis of the intestinal tract revealed upregulation of a host-defense gene signature, increased Reg3-γ and Defensin-α-4 in the teduglutide treated group compared to the vehicle treated group. these results indicate that treatment of GVHD mice the GLP-2 analogue, teduglutide, restores intestinal homeostasis with increased Paneth cells and antimicrobial peptides Overall design: BALB/c mice were pre-treated with theduglutide or vehicle twice a day for three days (d-3 to d-1). On d0 mice were lethal irradiated with 1000 cGy using a 137Cs source divided into two equal doses at 4 hours apart. After the second irradiation, mice were injected intravenously (i.v.) with 5x10e6 bone marrow cells together with 0.3 x 10e6 CD4+/CD8+ T cells from a C57BL/6 donor. Recipients were next treated with teduglutide or vehicle twice a day for 10 days after the allo-HCT. 4h after the last treatment the mice were sacrificed and Ileum samples were collected and processed to abtain RNA. RNA samples were further processed to perform microarray analysis, where we aim to obtain signifficant differences bwteen groups in relation to host defense gene sets.