Indole-3-carboxaldehyde (ICA) mitigates morbidity and mortality in a mouse model of Graft-versus-Host-Disease

ICA-treatment following allogeneic bone marrow transplant in mice limited GvHD pathology and GVHD mortality, augmented the integrity of the intestinal mucosal barrier, and limited production of inflammatory cytokines, but did not compromise donor T cell-mediated Graft vs. Leukemia (GvL) responses. Following protracted exposure, ICA treatment also induced donor-strain-specific tolerance of engrafted T cells. We used microarray to assess gene expression changes induced by ICA in the small intestine in animals with GvHD. Mice undergoing allogeneic bone marrow transplant (BMT) were treated daily with ICA starting one day prior to transplant and continuing until samples were harvested for RNA isolation on day 21 post-transplant. The transplant model used was C57Bl/6 donors and B10.BR recipients. On day -1, recipient mice received 11Gy lethal total body irradiation. On day 0, recipient mice were transplanted with 5 x 106 allogeneic T cell depleted BM (TCD-BM) cells, with or without 2 x 106 purified allogeneic T cells. Both TCD-BM only transplanted control animals, and TCD-BM + T cell transplanted animals, which develop GvHD, received a daily oral gavage of either 150 mg/kg ICA or Vehicle (DMSO (20%), PEG400 (40%), Citric Acid (2%)). Samples (ileum) were collected on day 21post-transplant.