Epidemiologic observations suggest that exposure to microbes in early life is associated with the prevention of diseases such as inflammatory bowel disease and asthma. In Science, Blumberg and colleagues show that more invariant natural killer cells (iNKT cells) accumulate in the lungs and colonic lamina propria and result in greater susceptibility to inflammatory bowel disease and asthma in germ-free mice than in specific pathogen–free mice. Exposure of neonatal germ-free mice to conventional microbiota normalizes the number of iNKT cells and results in less susceptibility to induced disease, but exposure of adult germ-free mice does not. The colons and lungs of adult germ-free mice have higher expression of CXCL16, a chemotactic factor for iNKT cells. Specific regions in Cxcl16 are hypermethylated in a tissue-specific way in germ-free mice, and colonization of neonatal mice with conventional microbiota reverses this epigenetic modification, but colonization of adult mice does not. The mechanisms by which the microbiota regulates CXCL16 expression and thus the accumulation of iNKT cells are unknown.

Science (22 March 2012) doi:10.1126/science.1219328