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

作者：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.

来源：Science, 2012, 336(6080): 489-493.

DOI：10.1126/science.1219328

• NKT CELLS
• AIRWAY INFLAMMATION
• ULCERATIVE-COLITIS
• HYGIENE HYPOTHESIS
• CHEMOKINE CXCL16
• RECOGNITION
• METHYLATION
• ACTIVATION
• EXPRESSION
• MODELS

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.

• 出版日期2012-4-27