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Sphingolipids from a Symbiotic Microbe Regulate Homeostasis of Host Intestinal Natural Killer T Cells
Open accessAbstract
Coevolution of beneficial microorganisms with the mammalian intestine fundamentally shapes mammalian physiology. Here, we report that the intestinal microbe Bacteroides fragilis modifies the homeostasis of host invariant natural killer T (iNKT) cells by supplementing the host's endogenous lipid antigen milieu with unique inhibitory sphingolipids. The process occurs early in life and effectively impedes iNKT cell proliferation during neonatal development. Consequently, total colonic iNKT cell numbers are restricted into adulthood, and hosts are protected against experimental iNKT cell-mediated, oxazolone-induced colitis. In studies with neonatal mice lacking access to bacterial sphingolipids, we found that treatment with B. fragilis glycosphingolipids-exemplified by an isolated peak (MW = 717.6) called GSL-Bf717-reduces colonic iNKT cell numbers and confers protection against oxazolone-induced colitis in adulthood. Our results suggest that the distinctive inhibitory capacity of GSL-Bf717 and similar molecules may prove useful in the treatment of autoimmune and allergic disorders in which iNKT cell activation is destructive.
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“Mono-colonization of neonatal GF mice with the commensal Bacteroides fragilis or exposure to a purified sphingolipid originating from B. fragilis was able to restore iNKT cell numbers in GF mice and to protect the animals from oxazolone-induced colitis.125”
From Interaction between microbiota and immunity in health and disease (2020) · cites this paper as [125]
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Metadata
- Authors
- An, D., Oh, S. F., Olszak, T., Neves, J. F., Avci, F. Y., Erturk-Hasdemir, D., Lu, X., Zeissig, S., Blumberg, R. S., & Kasper, D. L.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Blumberg, Richard S.
- Kasper, Dennis L.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 156
- Issue
- 1-2
- Pages
- 123-133
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3909465
- OpenAlex
- W1989478912
- Cited by
- 643
- References
- 42
- Citations by year
- 2026: 34 · 2025: 51 · 2024: 62 · 2023: 48 · 2022: 66 · 2021: 74 · 2020: 54 · 2019: 56 · 2018: 51 · 2017: 38 · 2016: 39 · 2015: 41 · 2014: 28
- FWCI
- 22.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Research Portal (King's College London) (submittedVersion, other-oa)
- Funders
- Crohn's and Colitis Foundation of America
- Brigham Young University
- Crohn's and Colitis Foundation (253712)
- University of Birmingham
- Stony Brook University
- National Institutes of Health (DK44319, DK034854, DK53056)
- Harvard Digestive Diseases Center, Harvard University (DK034854)
- National Institute of Allergy and Infectious Diseases (AI007061, AI090102, R21AI090102, T32AI007061)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK034854, DK51362, DK88199, DK 44319, DK53056, R01DK053056, R56DK053056, R37DK044319, R01DK051362, P30DK034854, R01DK044319, R01DK088199)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- Bacteroides fragilis, invariant natural killer T cells, sphingolipids, glycosphingolipids, gut microbiota, host-microbe coevolution, oxazolone-induced colitis, neonatal development, autoimmune disease, allergic diseases, lipid antigens
- MeSH terms
- Animals, Animals, Newborn, Bacteroides fragilis, Colitis, Colon, Glycosphingolipids, Mice, Inbred C57BL, Oxazolone, Cell Proliferation, Mice, Natural Killer T-Cells
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