| First Author | Koyama M | Year | 2023 |
| Journal | Immunity | Volume | 56 |
| Issue | 8 | Pages | 1876-1893.e8 |
| PubMed ID | 37480848 | Mgi Jnum | J:339314 |
| Mgi Id | MGI:7519971 | Doi | 10.1016/j.immuni.2023.06.024 |
| Citation | Koyama M, et al. (2023) Intestinal microbiota controls graft-versus-host disease independent of donor-host genetic disparity. Immunity 56(8):1876-1893.e8 |
| abstractText | Acute graft-versus-host disease (aGVHD) remains a major limitation of allogeneic stem cell transplantation (SCT), and severe intestinal manifestation is the major cause of early mortality. Intestinal microbiota control MHC class II (MHC-II) expression by ileal intestinal epithelial cells (IECs) that promote GVHD. Here, we demonstrated that genetically identical mice of differing vendor origins had markedly different intestinal microbiota and ileal MHC-II expression, resulting in discordant GVHD severity. We utilized cohousing and antibiotic treatment to characterize the bacterial taxa positively and negatively associated with MHC-II expression. A large proportion of bacterial MHC-II inducers were vancomycin sensitive, and peri-transplant oral vancomycin administration attenuated CD4(+) T cell-mediated GVHD. We identified a similar relationship between pre-transplant microbes, HLA class II expression, and both GVHD and mortality in a large clinical SCT cohort. These data highlight therapeutically tractable mechanisms by which pre-transplant microbial taxa contribute to GVHD independently of genetic disparity. |
