Cited by 643T-cell and B-cell ImmunologyGut microbiota and healthImmune Response and Inflammation

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Sphingolipids from a Symbiotic Microbe Regulate Homeostasis of Host Intestinal Natural Killer T Cells

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An, Dingding, Oh, Sungwhan F., Olszak, Torsten, Neves, Joana F., Avci, Fikri Y., Erturk-Hasdemir, Deniz, Lu, Xi, Zeissig, Sebastian, Blumberg, Richard S., Kasper, Dennis L.·2014·Cell

DOI 10.1016/j.cell.2013.11.042PMC PMC3909465

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Abstract

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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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: An, Dingding
Oh, Sungwhan F.
Neves, Joana F.
Avci, Fikri Y.
Lu, Xi
Zeissig, Sebastian
Blumberg, Richard S.
Kasper, Dennis L.
Venue: Cell
Publisher: Elsevier BV
Published: 2014-01
Volume: 156
Issue: 1-2
Pages: 123-133
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2013.11.042
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 462 d)
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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Sphingolipids from a Symbiotic Microbe Regulate Homeostasis of Host Intestinal Natural Killer T Cells

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