TY - JOUR T1 - Microbial exposure during early life has persistent effects on natural killer T cell function JF - Science Y1 - 2012 A1 - Olszak, Torsten A1 - An, Dingding A1 - Zeissig, Sebastian A1 - Vera, Miguel Pinilla A1 - Richter, Julia A1 - Franke, Andre A1 - Glickman, Jonathan N A1 - Siebert, Reiner A1 - Baron, Rebecca M A1 - Kasper, Dennis L A1 - Blumberg, Richard S KW - Aging KW - Animals KW - Animals, Newborn KW - Antigens, CD1d KW - Asthma KW - Bacteria KW - Chemokine CXCL16 KW - Chemokine CXCL6 KW - Colitis, Ulcerative KW - Colon KW - Disease Models, Animal KW - Disease Susceptibility KW - DNA Methylation KW - Germ-Free Life KW - Intestinal Mucosa KW - Intestines KW - Lung KW - Mice KW - Mice, Inbred C57BL KW - Natural Killer T-Cells KW - Oxazolone KW - Receptors, CXCR KW - Receptors, CXCR6 KW - Specific Pathogen-Free Organisms AB - 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. VL - 336 IS - 6080 U1 - http://www.ncbi.nlm.nih.gov/pubmed/22442383?dopt=Abstract ER -