An endogenous nanomineral chaperones luminal antigen and peptidoglycan to intestinal immune cells.

An endogenous nanomineral chaperones luminal antigen and peptidoglycan to intestinal immune cells.
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内源性纳米矿物伴侣将管腔抗原和肽聚糖与肠道免疫细胞结合。

DOI:
10.1038/nnano.2015.19
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发表时间:
2015-04
影响因子:
38.3
通讯作者:
--
中科院分区:
材料科学1区
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--
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在人类和其他哺乳动物中,已知钙离子和磷酸根离子从小肠远端分泌到管腔中。然而,为什么会发生这种分泌尚不清楚。在这里,我们表明,该过程导致形成无定形镁取代磷酸钙纳米颗粒,该纳米颗粒将可溶性大分子(例如细菌肽聚糖和口服喂养的蛋白质抗原)捕获在管腔中,并将它们转运至肠道组织的免疫细胞。含有大分子的纳米颗粒利用上皮 M 细胞进入派尔氏淋巴结——肠道中聚集着颗粒清除免疫细胞的小区域。在野生型小鼠中,含有这些天然形成的纳米颗粒的肠道免疫细胞表达免疫耐受相关分子“程序性死亡配体1(PD-L1)”,而在无法识别肽聚糖的NOD1/2双敲除小鼠中,PD-L1未被检测到。我们的结果解释了肠腔中组成型磷酸钙纳米颗粒的作用以及它如何帮助塑造肠道免疫稳态。
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 (PD-L1)’, whereas in NOD1/2 double knock-out mice, which cannot recognize peptidoglycan, PD-L1 was undetected. Our results explain a role for constitutively formed calcium phosphate nanoparticles in the gut lumen and how this helps to shape intestinal immune homeostasis.
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