title: Microbial exposure during early life has persistent effects on natural killer T cell function.
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.
authors.affiliation: Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Torsten
authors.initials: T
authors.lastname: Olszak
authors.forename: Dingding
authors.initials: D
authors.lastname: An
authors.forename: Sebastian
authors.initials: S
authors.lastname: Zeissig
authors.forename: Miguel Pinilla
authors.initials: MP
authors.lastname: Vera
authors.forename: Julia
authors.initials: J
authors.lastname: Richter
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Glickman
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Baron
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Kasper
authors.forename: Richard S
authors.initials: RS
authors.lastname: Blumberg
mesh_terms: D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D055610:Antigens, CD1d / Q000276:immunology; D001249:Asthma / Q000276:immunology*; D001419:Bacteria / Q000254:growth & development*; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6 / Q000235:genetics / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000276:immunology*; D003106:Colon / Q000276:immunology / Q000382:microbiology; D019175:DNA Methylation; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005856:Germ-Free Life; D007413:Intestinal Mucosa / Q000276:immunology*; D007422:Intestines / Q000276:immunology / Q000382:microbiology*; D008168:Lung / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000276:immunology*; D010081:Oxazolone; D054387:Receptors, CXCR / Q000235:genetics / Q000378:metabolism; D000075744:Receptors, CXCR6; D013047:Specific Pathogen-Free Organisms
chemical_list: D055610:Antigens, CD1d; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; C498926:Cxcl16 protein, mouse; C482906:Cxcr6 protein, mouse; D054387:Receptors, CXCR; D000075744:Receptors, CXCR6; D010081:Oxazolone