Notch2 signaling is required for proper mast cell distribution and mucosal immunity in the intestine.
Notch2 signaling is required for proper mast cell distribution and mucosal immunity in the intestine.
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DOI：
10.1182/blood-2010-07-289611
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发表时间：
2011-01
期刊：
影响因子：
20.3
通讯作者：
M. Sakata-Yanagimoto;Tôru Sakai;Yasuyuki Miyake;Toshiki I. Saito;H. Maruyama;Y. Morishita;Etsuko Nakagami-Yamaguchi;K. Kumano;H. Yagita;M. Fukayama;S. Ogawa;M. Kurokawa;K. Yasutomo;S. Chiba
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文献类型：
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作者：
M. Sakata-Yanagimoto;Tôru Sakai;Yasuyuki Miyake;Toshiki I. Saito;H. Maruyama;Y. Morishita;Etsuko Nakagami-Yamaguchi;K. Kumano;H. Yagita;M. Fukayama;S. Ogawa;M. Kurokawa;K. Yasutomo;S. Chiba
Notch受体介导的信号传导参与淋巴细胞的发育过程和功能调节，以及肥大细胞分化。在这里，我们调查是否Notch信号是必需的抗病原体宿主防御调节肥大细胞。肥大细胞很少发现在野生型C57 BL/6小鼠的小肠，但异常积累在固有层的Notch 2条件性敲除小鼠在幼稚状态的小肠粘膜。当移植到肥大细胞缺陷的W（sh）/W（sh）小鼠中时，Notch 2-null骨髓来源的肥大细胞很少在上皮层内发现，但异常地定位于固有层，而对照骨髓来源的肥大细胞主要在上皮层内发现。Notch 2基因敲除小鼠和对照小鼠感染委内瑞拉圆线虫L3期幼虫后，对照小鼠中大量肥大细胞迅速动员至上皮层。与此相反，肥大细胞大量积累在固有层的Notch 2条件敲除小鼠的小肠粘膜，伴随着受损的根除圆线虫委内瑞拉。这些发现表明，肥大细胞中的细胞自主Notch 2信号传导是肠肥大细胞的适当定位所必需的，并且进一步暗示Notch信号传导在小肠中的宿主-病原体界面中的关键作用。
Notch receptor-mediated signaling is involved in the developmental process and functional modulation of lymphocytes, as well as in mast cell differentiation. Here, we investigated whether Notch signaling is required for antipathogen host defense regulated by mast cells. Mast cells were rarely found in the small intestine of wild-type C57BL/6 mice but accumulated abnormally in the lamina propria of the small-intestinal mucosa of the Notch2-conditional knockout mice in naive status. When transplanted into mast cell-deficient W(sh)/W(sh) mice, Notch2-null bone marrow-derived mast cells were rarely found within the epithelial layer but abnormally localized to the lamina propria, whereas control bone marrow-derived mast cells were mainly found within the epithelial layer. After the infection of Notch2 knockout and control mice with L3 larvae of Strongyloides venezuelensis, the abundant number of mast cells was rapidly mobilized to the epithelial layer in the control mice. In contrast, mast cells were massively accumulated in the lamina propria of the small intestinal mucosa in Notch2-conditional knockout mice, accompanied by impaired eradication of Strongyloides venezuelensis. These findings indicate that cell-autonomous Notch2 signaling in mast cells is required for proper localization of intestinal mast cells and further imply a critical role of Notch signaling in the host-pathogen interface in the small intestine.