Notch-1 signaling regulates intestinal epithelial barrier function, through interaction with CD4+ T cells, in mice and humans.
Notch-1 signaling regulates intestinal epithelial barrier function, through interaction with CD4+ T cells, in mice and humans.
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DOI：
10.1053/j.gastro.2010.10.057
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发表时间：
2011-02
期刊：
影响因子：
29.4
通讯作者：
Mayer L
中科院分区：
文献类型：
--
作者：
Dahan S;Rabinowitz KM;Martin AP;Berin MC;Unkeless JC;Mayer L
淋巴细胞和肠上皮细胞（IECs）之间的相互作用发生在胃肠道的亚上皮间隙。正常人固有层淋巴细胞（LPLs）诱导IECs分化。在小鼠（如RAG1−/−小鼠）中，LPLs缺失导致上皮细胞分化缺陷。我们研究了淋巴上皮相互作用在上皮分化和屏障功能中的作用。我们使用过继性转移来确定CD4+ T细胞（CD4+CD62L+CD45RbHi和/或CD4+CD62L+CD45RbLo）是否可以克服渗透性缺陷（在Ussing室中量化）。免疫荧光染色检测小鼠和人结肠样品中cleaved Notch-1、villin和claudin-5的表达。Caco-2细胞被含有特定Notch-1或打乱shRNA序列的慢病毒感染。通过免疫印迹和免疫荧光分析紧密连接组装，并监测经上皮耐药。在RAG1−/−结肠细胞中未检测到裂解的Notch-1、villin或claudin-5的表达；它们的丧失与肠道通透性增加有关。将CD45RbHi和/或CD45RbLow细胞转移到RAG1−/−小鼠体内，可诱导结肠细胞中裂解的Notch、绒毛蛋白和claudin-5的表达，并显著降低远端结肠的通透性。Caco-2细胞中Notch-1表达的缺失与跨上皮抗性降低以及紧密连接蛋白的表达和定位失调相关。克罗恩病患者结肠上皮中切割的Notch-1水平升高。LPLs促进粘膜屏障功能，这与Notch-1信号通路的激活有关。LPLs通过诱导IEC分化、极化和屏障功能维持肠道内稳态。
Interactions between lymphocytes and intestinal epithelial cells (IECs) occur in the sub-epithelial space of the gastrointestinal tract. Normal human lamina propria lymphocytes (LPLs) induce differentiation of IECs. The absence of LPLs in mice, such as in RAG1−/− mice, results in defect in epithelial cell differentiation. We investigated the role of lympho–epithelial interactions in epithelial differentiation and barrier function. We used adoptive transfer to determine if CD4+ T cells (CD4+CD62L+CD45RbHi and/or CD4+CD62L+CD45RbLo) could overcome permeability defect (quantified in Ussing chambers). Immunofluorescence staining was performed to determine expression of cleaved Notch-1, villin, and claudin-5 in colon samples from mice and humans. Caco-2 cells were infected with a lentivirus containing a specific Notch-1 or scrambled shRNA sequence. Tight junction assembly was analyzed by immunoblot and immunofluorescence analyses and transepithelial resistance was monitored. Expression of cleaved Notch-1, villin, or claudin-5 was not detected in RAG1−/− colonocytes; their loss correlated with increased intestinal permeability. Transfer of CD45RbHi and/or CD45RbLow cells into RAG1−/− mice induced expression of cleaved Notch, villin, and claudin-5 in colonocytes and significantly reduced the permeability of the distal colon. Loss of Notch-1 expression in Caco-2 cells correlated with decreased trans-epithelial resistance and dysregulated expression and localization of tight junction proteins. Levels of cleaved Notch-1 were increased in colonic epithelium of patients with Crohn’s disease. LPLs promote mucosal barrier function, which is associated with activation of the Notch-1 signaling pathway. LPLs maintain intestinal homeostasis by inducing IEC differentiation, polarization, and barrier function.
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DOI：
10.1152/ajpgi.00037.2005
发表时间：
2005-08-01
影响因子：
4.5
作者：
Alkhoury, F;Malo, MS;Hodin, RA
通讯作者：
Hodin, RA
DOI：
10.1083/jcb.200311021
发表时间：
2004-07-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Blache P;van de Wetering M;Duluc I;Domon C;Berta P;Freund JN;Clevers H;Jay P
通讯作者：
Jay P
影响因子：
4.9
作者：
Roda, Giulia;Dahan, Stephanie;Mezzanotte, Laura;Caponi, Alessandra;Roth-Walter, Franziska;Pinn, David;Mayer, Lloyd
通讯作者：
Mayer, Lloyd
影响因子：
4.4
作者：
POWRIE, F;LEACH, MW;COFFMAN, RL
通讯作者：
COFFMAN, RL
影响因子：
56.9
作者：
Kerneis, S;Bogdanova, A;Pringault, E
通讯作者：
Pringault, E