Crucial role of plasmacytoid dendritic cells in the development of acute colitis through the regulation of intestinal inflammation
Crucial role of plasmacytoid dendritic cells in the development of acute colitis through the regulation of intestinal inflammation
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DOI：
10.1038/mi.2016.96
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发表时间：
2017-07-01
影响因子：
8
通讯作者：
Sato, K.
中科院分区：
文献类型：
--
作者：
Arimura, K.;Takagi, H.;Sato, K.
肠道内稳态的破坏可导致炎症性肠病，赋予易感基因和环境因素影响肠道内聚集和激活致大肠杆菌吞噬细胞。浆细胞样树突状细胞（Plasmacytoid dendritic cells，pDC）是一种免疫细胞，通过大量分泌I型干扰素（type I interferon，IFN-I）来控制先天性和适应性免疫。然而，pDC对肠道炎症进展的贡献仍不清楚。在这里，我们显示了一个关键的作用，pDC在急性结肠炎的启动使用T细胞非依赖性急性结肠炎模型与pDC的选择性消融。尽管pDC在粘膜损伤后在发炎的结肠中积累，但pDC的缺乏减弱了不依赖于IFN-I信号传导的急性结肠炎的发展，伴随着促炎细胞因子的结肠产生减少。此外，pDC的缺乏损害了致结肠炎性吞噬细胞进入发炎结肠的动员，这可能是由C-C趋化因子受体2配体的粘膜产生被消除介导的。因此，我们的研究结果强调了pDC在诱导结肠炎症中的关键作用，其调节炎性吞噬细胞的结肠积聚，导致急性结肠炎的开始和恶化，并且它们可能在控制肠道粘膜免疫稳态中起关键作用。
Disruption of intestinal homeostasis can lead to inflammatory bowel diseases endowed susceptibility genes and environmental factors affecting intestinal accumulation and activation of colitogenic phagocytes. Plasmacytoid dendritic cells (pDCs) are immune cells that had been proposed to control innate and adaptive immunity through the massive secretion of type I interferon (IFN-I). However, the contribution of pDCs to the progression of intestinal inflammation remains unclear. Here we show a critical role of pDCs in the initiation of acute colonic inflammation using T-cell-independent acute colitis model with a selective ablation of pDCs. Although pDCs accumulated in the inflamed colon upon mucosal injury, deficiency of pDCs attenuated the development of acute colitis independent of IFN-I signaling, accompanied by the diminished colonic production of proinflammatory cytokines. Furthermore, deficiency of pDCs impaired the mobilization of colitogenic phagocytes into the inflamed colon possibly mediated by the abrogated mucosal production of C-C chemokine receptor 2 ligand. Thus, our findings highlight a critical role of pDCs in the induction of the colonic inflammation that regulates the colonic accumulation of inflammatory phagocytes leading to the initiation and exacerbation of acute colitis, and they may serve a key role in controlling gut mucosal immune homeostasis.