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Microbial Exposure During Early Life Has Persistent Effects on Natural Killer T Cell Function

2012; American Association for the Advancement of Science; Volume: 336; Issue: 6080 Linguagem: Inglês

10.1126/science.1219328

1095-9203

Torsten Olszak, Dingding An, Sebastian Zeißig, Miguel Pinilla-Vera, Julia Richter, André Franke, Jonathan N. Glickman, Reiner Siebert, Rebecca M. Baron, Dennis L. Kasper, Richard S. Blumberg,

T-cell and B-cell Immunology

Exposure to microbes during early childhood is associated with protection from immune-mediated diseases such as inflammatory bowel disease (IBD) and asthma. Here, we show that in germ-free (GF) mice, invariant natural killer T (iNKT) cells accumulate in the colonic lamina propria and lung, resulting in increased morbidity in models of IBD and allergic asthma as compared with that of specific pathogen-free mice. This was associated with increased intestinal and pulmonary expression of the chemokine ligand CXCL16, which was associated with increased mucosal iNKT cells. Colonization of neonatal-but not adult-GF mice with a conventional microbiota protected the animals from mucosal iNKT accumulation and related pathology. These results indicate that age-sensitive contact with commensal microbes is critical for establishing mucosal iNKT cell tolerance to later environmental exposures.