期刊
NATURE NANOTECHNOLOGY
卷 10, 期 4, 页码 361-369出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/NNANO.2015.19
关键词
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资金
- UK Medical Research Council [U105960399]
- UK Engineering and Physical Sciences Research Council [GR/R50097]
- Dairy Council
- Sir Halley Stewart Trust
- Dutch MS Research Foundation
- European Union [312483-ESTEEM2]
- European Research Council [291,522 3DIMAGE]
- Biological and Biotechnological Research Council [BB/J014762/1, BB/K021257/1]
- National Institutes of Health [DK064730, AI111388]
- BBSRC [BBS/E/D/20231762, BBS/E/D/20231759, BB/K021257/1, BB/J014672/1] Funding Source: UKRI
- EPSRC [EP/E059678/1, EP/D032210/1] Funding Source: UKRI
- MRC [MC_U105960399] Funding Source: UKRI
- STFC [ST/N002423/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/K021257/1, BB/J014672/1, BBS/E/D/20231762, BBS/E/D/20231759] Funding Source: researchfish
- Engineering and Physical Sciences Research Council [EP/D032210/1, EP/E059678/1] Funding Source: researchfish
- Medical Research Council [MC_U105960399, MR/J006742/1] Funding Source: researchfish
- Science and Technology Facilities Council [ST/N002423/1] Funding Source: researchfish
In humans and other mammals it is known that calcium and phosphate ions are secreted from the distal small intestine into the lumen. However, why this secretion occurs is unclear. Here, we show that the process leads to the formation of amorphous magnesium-substituted calcium phosphate nanoparticles that trap soluble macromolecules, such as bacterial peptidoglycan and orally fed protein antigens, in the lumen and transport them to immune cells of the intestinal tissue. The macromolecule-containing nanoparticles utilize epithelial M cells to enter Peyer's patches, small areas of the intestine concentrated with particle-scavenging immune cells. In wild-type mice, intestinal immune cells containing these naturally formed nanoparticles expressed the immune tolerance-associated molecule 'programmed death-ligand 1', whereas in NOD1/2 double knockout mice, which cannot recognize peptidoglycan, programmed death-ligand 1 was undetected. Our results explain a role for constitutively formed calcium phosphate nanoparticles in the gut lumen and show how this helps to shape intestinal immune homeostasis.
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