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Cell. 2014 Jan 16;156(1-2):123-33. doi: 10.1016/j.cell.2013.11.042.

Sphingolipids from a symbiotic microbe regulate homeostasis of host intestinal natural killer T cells.

Author information

1
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
2
Division of Gastroenterology, Hepatology, and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
3
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA; Department of Biochemistry and Molecular Biology, Center for Molecular Medicine, University of Georgia, Athens, GA 30602, USA.
4
Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
5
Division of Gastroenterology, Hepatology, and Endoscopy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: rblumberg@partners.org.
6
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: dennis_kasper@hms.harvard.edu.

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.

PMID:
24439373
PMCID:
PMC3909465
DOI:
10.1016/j.cell.2013.11.042
[Indexed for MEDLINE]
Free PMC Article

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