E-NPP3 controls plasmacytoid dendritic cell numbers in the small intestine.
E-NPP3 controls plasmacytoid dendritic cell numbers in the small intestine.
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DOI：
10.1371/journal.pone.0172509
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Takeda K
中科院分区：
文献类型：
--
作者：
Furuta Y;Tsai SH;Kinoshita M;Fujimoto K;Okumura R;Umemoto E;Kurashima Y;Kiyono H;Kayama H;Takeda K
细胞外腺苷5 '-三磷酸（ATP）执行多种功能，包括激活和诱导许多细胞类型的凋亡。ATP水解胞外酶胞外核苷酸焦磷酸酶/磷酸二酯酶3（E-NPP 3）通过肥大细胞和嗜碱性粒细胞调节ATP依赖性慢性过敏反应。然而，E-NPP 3也在小肠的上皮细胞上高度表达。在这项研究中，我们表明E-NPP 3通过调节肠道细胞外ATP来控制肠道中浆细胞样树突状细胞（pDC）的数量。在Enpp 3-/-小鼠中，肠腔中的ATP浓度增加。pDC数量在小肠固有层和派伊尔集合淋巴结中显著减少。Enpp 3-/-小鼠的肠pDC显示增强的细胞死亡，其特征在于膜联蛋白V结合和裂解的半胱天冬酶-3的表达增加。与常规DC相比，pDC对ATP诱导的细胞死亡高度敏感。ATP诱导的细胞死亡在P2 rx 7-/-pDC中被消除。因此，在Enpp 3-/-P2 rx 7-/-小鼠中恢复了肠pDC的数量。这些发现表明E-NPP 3调节ATP浓度，从而防止小肠中pDC的减少。
Extracellular adenosine 5’-triphosphate (ATP) performs multiple functions including activation and induction of apoptosis of many cell types. The ATP-hydrolyzing ectoenzyme ecto-nucleotide pyrophosphatase/phosphodiesterase 3 (E-NPP3) regulates ATP-dependent chronic allergic responses by mast cells and basophils. However, E-NPP3 is also highly expressed on epithelial cells of the small intestine. In this study, we showed that E-NPP3 controls plasmacytoid dendritic cell (pDC) numbers in the intestine through regulation of intestinal extracellular ATP. In Enpp3-/- mice, ATP concentrations were increased in the intestinal lumen. pDC numbers were remarkably decreased in the small intestinal lamina propria and Peyer’s patches. Intestinal pDCs of Enpp3-/- mice showed enhanced cell death as characterized by increases in annexin V binding and expression of cleaved caspase-3. pDCs were highly sensitive to ATP-induced cell death compared with conventional DCs. ATP-induced cell death was abrogated in P2rx7-/- pDCs. Accordingly, the number of intestinal pDCs was restored in Enpp3-/- P2rx7-/- mice. These findings demonstrate that E-NPP3 regulates ATP concentration and thereby prevents the decrease of pDCs in the small intestine.