Intestinal microbiota controls graft-versus-host disease independent of donor-host genetic disparity Journal Article

   


Authors: Koyama, M.; Hippe, D. S.; Srinivasan, S.; Proll, S. C.; Miltiadous, O.; Li, N.; Zhang, P.; Ensbey, K. S.; Hoffman, N. G.; Schmidt, C. R.; Yeh, A. C.; Minnie, S. A.; Strenk, S. M.; Fiedler, T. L.; Hattangady, N.; Kowalsky, J.; Grady, W. M.; Degli-Esposti, M. A.; Varelias, A.; Clouston, A. D.; van den Brink, M. R. M.; Dey, N.; Randolph, T. W.; Markey, K. A.; Fredricks, D. N.; Hill, G. R.
Article Title: Intestinal microbiota controls graft-versus-host disease independent of donor-host genetic disparity
Abstract: 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. © 2023 Elsevier Inc.
Keywords: transplantation, homologous; mouse; animal; animals; mice; hematopoietic stem cell transplantation; graft versus host reaction; vancomycin; intestine flora; gvhd; graft vs host disease; allotransplantation; antibiotics; graft-versus-host disease; procedures; microbiota; interferon-γ; gastrointestinal microbiome; intestinal epithelial cells; mhc class ii antigen presentation
Journal Title: Immunity
Volume: 56
Issue: 8
ISSN: 1074-7613
Publisher: Cell Press  
Date Published: 2023-08-08
Start Page: 1876
End Page: 1893.e8
Language: English
DOI: 10.1016/j.immuni.2023.06.024
PUBMED: 37480848
PROVIDER: scopus
PMCID: PMC10530372
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85166906791&doi=10.1016%2fj.immuni.2023.06.024&partnerID=40&md5=6be9a0e4f01b97bc1c4ff6496381d603
Notes: Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- Source: Scopus
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MSK Authors
  1. Marcel R M Van Den Brink
    616 Van Den Brink
  2. Oriana Miltiadous
    16 Miltiadous
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