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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Hausmann, Martin Rogler, Gerhard Hennet, Thierry Kurakevich, Ekaterina Borsig, Lubor |
| Description | Author Affiliation: Kurakevich E ( Institute of Physiology and Zürich Center for Integrative Human Physiology, University of Zürich, 8057 Zürich, Switzerland.); |
| Abstract | Breast milk oligosaccharides shape the intestinal environment by affecting mucosal immunity and bacterial colonization. To clarify the role of milk oligosaccharide sialyl( 2,3)lactose (3SL) in intestinal physiology and disease, we investigated colitis development in Il10(-/-) mice exposed to normal or 3SL-deficient milk during lactation. Onset and progression of intestinal inflammation were delayed in Il10(-/-) mice deficient for the 2,3 sialyltransferase 4 (ST3GAL4) responsible for 3SL biosynthesis. The proinflammatory role of 3SL was confirmed by showing that oral supplementation of newborn Il10(-/-);St3gal4(-/-) mice with 3SL increased colitis severity. Conversely, fostering of newborn Il10(-/-) mice to lactating St3gal4(-/-) mothers reduced colitis severity. 3SL directly stimulated mesenteric lymph node CD11c(+) dendritic cells and induced production of cytokines required for expansion of TH1 and TH17 T cells. The stimulatory effect of 3SL was attenuated in Tlr4-deficient CD11c(+) cells, demonstrating that 3SL induces inflammation through Toll-like receptor 4 (TLR4) signaling. Thus, 3SL directly modulates mucosal immunity, which increases susceptibility to colitis. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 43 |
| Volume Number | 110 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2013-10-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Antigens, CD11c Immunology Intestines Lactose Analogs & Derivatives Sialic Acids Toll-Like Receptor 4 Animals Animals, Newborn Metabolism Bacteria Classification Genetics Cells, Cultured Colitis Cytokines Dendritic Cells Flow Cytometry Gastrointestinal Tract Microbiology Pathology Gene Expression Immunity, Mucosal Interleukin-10 Deficiency Cytology Lactation Mice Mice, Inbred C57BL Mice, Knockout Chemistry Reverse Transcriptase Polymerase Chain Reaction Sialyltransferases Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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