Cell
Volume 156, Issues 1–2, 16 January 2014, Pages 123-133
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Article
Sphingolipids from a Symbiotic Microbe Regulate Homeostasis of Host Intestinal Natural Killer T Cells

https://doi.org/10.1016/j.cell.2013.11.042Get rights and content
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Highlights

  • Symbiotic bacterial glycosphingolipids modulate host iNKT cell homeostasis

  • Early exposure to these lipids protects the host from later colitis challenges

  • These lipids inhibit iNKT cell proliferation

  • Treatment with microbial sphingolipids protects the host from colitis

Summary

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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Present address: Department of Internal Medicine I, University Medical Center Schleswig-Holstein, Kiel 24105, Germany