Microbial Ecology in States of Health and Disease Workshop Summary (2014) / Chapter Skim
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A4 Microbial exposure during early life has persistent effects on natural killer T Cell function--Torsten Olszak, Dingding An, Sebastian Zeissig, Miguel Penilla Vera, Julia Richter, Andre Franke, Jonathan N. Glickman, Reiner Siebert, Rebecca M. Barron, Dennis L. Kasper, and Richard S. Blumberg
A4 Microbial exposure during early life has persistent effects on natural killer T Cell function--Torsten Olszak, Dingding An, Sebastian Zeissig, Miguel Penilla Vera, Julia Richter, Andre Franke, Jonathan N. Glickman, Reiner Siebert, Rebecca M. Barron, Dennis L. Kasper, and Richard S. Blumberg
Pages 153-163
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mice, invariant natural killer T (iNKT) cells accumulate in the colonic lamina propria and 9 From "Microbial exposure during early life has persistent effects on natural killer T cell function," Science 336(6080)
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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.
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(D) Percentages of colonic iNKT cells of live LP lymphocytes in gender-matched SPF and GF mice were analyzed at different ages by means of flow cytometry (n = 4 mice per group)
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Indeed, when we colonized pregnant GF female mice just before delivery and therefore exposed neonatal GF mice to SPF conditions on their first day of life (GF/n) , we observed a complete normalization of iNKT cell levels that persisted even two months after colonization (Figure A4-2D)
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(GF/a) mice were GF mice that were exposed to SPF environmental conditions at the age of 5 weeks and maintained for 4 more weeks.
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We observed that similar to the colon, GF mice developed an allergic airway response to OVA significantly greater than that observed in SPF mice, as demonstrated by increases in airway resistance, total bronchial alveolar lavage fluid (BALF) cell numbers, BALF eosinophilia, serum immunoglobulin E (IgE)
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All data were obtained from more than two independent experiments with similar results. Error bars indicate the SD.
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(C) Colon, ileum, and lung tissue samples were analyzed from age-matched SPF and GF mice at different time points for Cxcl16 expression (n = 5 mice per group)
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so as to force Cxcl16 methylation. Compared with PBS-treated control mice, folinic acid administration resulted in elevated methylation of the Cxcl16 gene in the colon, ileum, and lung; at least a three- to fourfold increase of Cxcl16 mRNA expression in the same tissues; increased CXCL16 serum levels; and accumulation of iNKT cells in these tissues as observed in GF mice (fig.
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Troy and S Edwards for handling of the GF mice, J
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G Wingender et al., Invariant NKT cells are required for airway inflammation induced by environ mental antigens.
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