E-NPP3 controls plasmacytoid dendritic cell numbers in the small intestineReport as inadecuate




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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.



Author: Yoki Furuta , Shih-Han Tsai , Makoto Kinoshita, Kosuke Fujimoto, Ryu Okumura, Eiji Umemoto, Yosuke Kurashima, Hiroshi Kiyono, His

Source: http://plos.srce.hr/



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