Microbial exposure during early life has persistent effects on natural killer T cell function.

Authors:
Torsten Olszak, Dingding An, Sebastian Zeissig, Miguel Pinilla Vera, Julia Richter, Andre Franke, Jonathan N Glickman, Reiner Siebert, Rebecca M Baron, Dennis L Kasper, Richard S Blumberg
Year of publication:
2012
Volume:
336
Issue:
6080
Issn:
0036-8075
Journal title abbreviated:
SCIENCE
Journal title long:
Science : a weekly journal devoted to the advancement of science / American Association for the Advancement of Science
Impact factor:
34.661
Abstract:
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.