Ambient oxygen levels regulate intestinal dysbiosis and GVHD severity after allogeneic stem cell transplantation.

Animals Mice Dysbiosis Hematopoietic Stem Cell Transplantation Intestines / pathology Graft vs Host Disease / pathology Gastrointestinal Diseases
T cell-mediated gastrointestinal (GI) diseases allogeneic germ-free graft-versus-host host disease hypoxia iron chelation microbiome oxygen tissue tolerance transplantation

Journal

Immunity
ISSN: 1097-4180
Titre abrégé: Immunity
Pays: United States
ID NLM: 9432918

Informations de publication

Date de publication:
14 02 2023
Historique:
received: 10 06 2022
revised: 12 11 2022
accepted: 10 01 2023
pubmed: 4 2 2023
medline: 18 2 2023
entrez: 3 2 2023
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.immuni.2023.01.007 PMID: 36736321
pubmed: 36736321
pii: S1074-7613(23)00017-1
doi: 10.1016/j.immuni.2023.01.007
pii:
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

353-368.e6

Subventions

Organisme : NCI NIH HHS
ID : R01 CA228308
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL123340
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL149633
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA023766
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA245546
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL147584
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA228358
Pays : United States

Informations de copyright

Copyright © 2023 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Keisuke Seike (K)

Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Rogel Cancer Center, Ann Arbor, MI, USA.

Anders Kiledal (A)

Department of Earth & Environmental Sciences, University of Michigan, Ann Arbor, MI 48109, USA.

Hideaki Fujiwara (H)

Department of Hematology and Oncology, Okayama University Hospital, 2-5-1, Shikata-cho, Kita-ku, Okayama 700-8558, Japan.

Israel Henig (I)

Department of Hematology, Rambam Health Care Campus, Haifa, Israel.

Marina Burgos da Silva (M)

Department of Immunology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

Marcel R M van den Brink (MRM)

Department of Immunology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

Robert Hein (R)

Department of Earth & Environmental Sciences, University of Michigan, Ann Arbor, MI 48109, USA.

Matthew Hoostal (M)

Department of Internal Medicine, Division of Infectious Disease, University of Michigan Health System, Ann Arbor, MI, USA.

Chen Liu (C)

Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.

Katherine Oravecz-Wilson (K)

Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Rogel Cancer Center, Ann Arbor, MI, USA.

Emma Lauder (E)

Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Rogel Cancer Center, Ann Arbor, MI, USA.

Lu Li (L)

Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Rogel Cancer Center, Ann Arbor, MI, USA.

Yaping Sun (Y)

Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Rogel Cancer Center, Ann Arbor, MI, USA.

Thomas M Schmidt (TM)

Department of Internal Medicine, Division of Infectious Disease, University of Michigan Health System, Ann Arbor, MI, USA.

Yatrik M Shah (YM)

Department of Internal Medicine, Division of Gastroenterology, University of Michigan Health System, Ann Arbor, MI, USA; Department of Molecular and Integrative Physiology, University of Michigan School of Medicine, Ann Arbor, MI, USA.

Robert R Jenq (RR)

Department of Genomic Medicine, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX, USA.

Gregory Dick (G)

Department of Earth & Environmental Sciences, University of Michigan, Ann Arbor, MI 48109, USA.

Pavan Reddy (P)

Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Rogel Cancer Center, Ann Arbor, MI, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA. Electronic address: pavan.reddy@bcm.edu.

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Classifications MeSH

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questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Dysbiose › Ambient oxygen levels regulate intestinal...
questionsmedicales.fr › Procédures de chirurgie opératoire › Transplantation › Transplantation cellulaire › Transplantation de cellules souches › Transplantation de cellules souches hématopoïétiques › Ambient oxygen levels regulate intestinal...
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