Ambient oxygen levels regulate intestinal dysbiosis and GVHD severity after allogeneic stem cell transplantation Journal Article
| Authors: | Seike, K.; Kiledal, A.; Fujiwara, H.; Henig, I.; Burgos da Silva, M.; van den Brink, M. R. M.; Hein, R.; Hoostal, M.; Liu, C.; Oravecz-Wilson, K.; Lauder, E.; Li, L.; Sun, Y.; Schmidt, T. M.; Shah, Y. M.; Jenq, R. R.; Dick, G.; Reddy, P. |
| Article Title: | Ambient oxygen levels regulate intestinal dysbiosis and GVHD severity after allogeneic stem cell transplantation |
| Abstract: | The severity of T cell-mediated gastrointestinal (GI) diseases such as graft-versus-host disease (GVHD) and inflammatory bowel diseases correlates with a decrease in the diversity of the host gut microbiome composition characterized by loss of obligate anaerobic commensals. The mechanisms underpinning these changes in the microbial structure remain unknown. Here, we show in multiple specific pathogen-free (SPF), gnotobiotic, and germ-free murine models of GI GVHD that the initiation of the intestinal damage by the pathogenic T cells altered ambient oxygen levels in the GI tract and caused dysbiosis. The change in oxygen levels contributed to the severity of intestinal pathology in a host intestinal HIF-1α- and a microbiome-dependent manner. Regulation of intestinal ambient oxygen levels with oral iron chelation mitigated dysbiosis and reduced the severity of the GI GVHD. Thus, targeting ambient intestinal oxygen levels may represent a novel, non-immunosuppressive strategy to mitigate T cell-driven intestinal diseases. © 2023 Elsevier Inc. |
| Keywords: | mouse; animal; animals; mice; oxygen; hematopoietic stem cell transplantation; pathology; transplantation; hypoxia; graft versus host reaction; graft vs host disease; gastrointestinal disease; intestine; intestines; gastrointestinal diseases; iron chelation; allogeneic; microbiome; tissue tolerance; dysbiosis; germ-free; graft-versus-host host disease; t cell-mediated gastrointestinal (gi) diseases |
| Journal Title: | Immunity |
| Volume: | 56 |
| Issue: | 2 |
| ISSN: | 1074-7613 |
| Publisher: | Cell Press |
| Date Published: | 2023-02-14 |
| Start Page: | 353 |
| End Page: | 368.e6 |
| Language: | English |
| DOI: | 10.1016/j.immuni.2023.01.007 |
| PUBMED: | 36736321 |
| PROVIDER: | scopus |
| PMCID: | PMC11098523 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in PubMed and PDF -- Source: Scopus |
