期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2013
卷号：110
期号：43
页码：17444-17449
DOI：10.1073/pnas.1306322110
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
