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

• Published in: Science (American Association for the Advancement of Science) Vol. 336; no. 6080; pp. 489 - 493
• Main Authors: Olszak, Torsten, An, Dingding, Zeissig, Sebastian, Vera, Miguel Pinilla, Richter, Julia, Franke, Andre, Glickman, Jonathan N., Siebert, Reiner, Baron, Rebecca M., Kasper, Dennis L., Blumberg, Richard S.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 27.04.2012; The American Association for the Advancement of Science
• Subjects: Aging; Animal models; Animals; Animals, Newborn; Antigens, CD1d - immunology; Asthma; Asthma - immunology; Bacteria - growth & development; Biological and medical sciences; Chemokine CXCL16; Chemokine CXCL6 - genetics; Chemokine CXCL6 - metabolism; Children & youth; Colitis; Colitis, Ulcerative - chemically induced; Colitis, Ulcerative - immunology; Colon - immunology; Colon - microbiology; Disease Models, Animal; Disease Susceptibility; DNA; DNA Methylation; Epidemiology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genetics of the immune response; Germ-Free Life; Ileum; Immune system; Immunobiology; Inflammatory bowel diseases; Inflammatory diseases; Intestinal Mucosa - immunology; Intestines - immunology; Intestines - microbiology; Lung - immunology; Lungs; Lymphocytes; Mice; Mice, Inbred C57BL; Microbiota; Microorganisms; Natural killer T cells; Natural Killer T-Cells - immunology; Oxazolone; Pathology; Receptors, CXCR - genetics; Receptors, CXCR - metabolism; Receptors, CXCR6; Specific Pathogen-Free Organisms; Young Children; Immunoprotection; Vertebrata; Mammalia; Mouse; Rodentia; Early; Exposure; NKT cell
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1219328

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.