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Bifidobacterium alters the gut microbiota and modulates the functional metabolism of T regulatory cells in the context of immune checkpoint blockade.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2020 Nov 03; Vol. 117 (44), pp. 27509-27515. Date of Electronic Publication: 2020 Oct 19. - Publication Year :
- 2020
-
Abstract
- Immune checkpoint-blocking antibodies that attenuate immune tolerance have been used to effectively treat cancer, but they can also trigger severe immune-related adverse events. Previously, we found that Bifidobacterium could mitigate intestinal immunopathology in the context of CTLA-4 blockade in mice. Here we examined the mechanism underlying this process. We found that Bifidobacterium altered the composition of the gut microbiota systematically in a regulatory T cell (Treg)-dependent manner. Moreover, this altered commensal community enhanced both the mitochondrial fitness and the IL-10-mediated suppressive functions of intestinal Tregs, contributing to the amelioration of colitis during immune checkpoint blockade.<br />Competing Interests: The authors declare no competing interest.<br /> (Copyright © 2020 the Author(s). Published by PNAS.)
- Subjects :
- Animals
Autoimmune Diseases chemically induced
Autoimmune Diseases immunology
CTLA-4 Antigen antagonists & inhibitors
CTLA-4 Antigen metabolism
Disease Models, Animal
Female
Humans
Immune Checkpoint Inhibitors adverse effects
Immune Tolerance
Interleukin-10 genetics
Interleukin-10 metabolism
Mice
Mice, Knockout
T-Lymphocytes, Regulatory metabolism
Autoimmune Diseases prevention & control
Bifidobacterium immunology
Gastrointestinal Microbiome immunology
Probiotics administration & dosage
T-Lymphocytes, Regulatory immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 117
- Issue :
- 44
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 33077598
- Full Text :
- https://doi.org/10.1073/pnas.1921223117