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Dingding An, Torsten Olszak, Sebastian Zeissig, Richard Blumberg, Dennis Kasper, Early life exposure to microbiota has persistent effects on colonic lamina propria iNKT cells and colitis: P-193., Inflammatory Bowel Diseases, Volume 17, Issue Suppl_2, 1 December 2011, Page S70, https://doi.org/10.1097/00054725-201112002-00227
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As an essential contributor to a number of autoimmune diseases, invariant natural killer T (iNKT) cells upon activation can rapidly release substantial quantities of cytokines and chemokines and thus shape the functions of other immune cells. In this study, we used an iNKT cell-mediated oxazolone ulcerative colitis model and found that germ-free (GF) mice develop a severe colitis phenotype while conventionally raised mice were completely protected. The protection of GF mice in this model can be restored only when the mice were exposed to the conventional microflora at birth but not at weaning. We also found that the severe colitis phenotype in GF mice was due to heightened iNKT cell numbers in the colonic lamina propia and the disease was CD1d-dependent. Mechanistically, the accumulation of iNKT cells was at least partially associated with increased intestinal expression of the chemokine ligand CXCL16, which leads to CXCR6-dependent iNKT cell recruitment. These results provide one piece of direct biologic evidence supporting conclusions from numerous epidemiologic studies that early life exposure to microbes profoundly influences the maturation of immune system and increases the tolerance to certain environmental stimuli that may provoke autoimmune diseases later in life.
