肥大细胞通过糜蛋白酶/Mcpt4 依赖性机制调节肠道上皮的稳态迁移和屏障功能。
Mast cells regulate homeostatic intestinal epithelial migration and barrier function by a chymase/Mcpt4-dependent mechanism.
机构信息
Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
出版信息
Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22381-6. doi: 10.1073/pnas.0906372106. Epub 2009 Dec 16.
Abstract
Altered intestinal barrier function is postulated to be a central predisposing factor to intestinal diseases, including inflammatory bowel diseases and food allergies. However, the mechanisms involved in maintaining homeostatic intestinal barrier integrity remain undefined. In this study, we demonstrate that mice deficient in mast cells (Kit(W-sh/W-sh) [Wsh]) or mast cell chymase (Mcpt4(-/-)) have significantly decreased basal small intestinal permeability compared with wild-type (WT) mice. Altered intestinal barrier function was linked to decreased intestinal epithelial cell migration along the villus/crypt axis, altered intestinal morphology, and dysregulated claudin-3 crypt expression. Remarkably, engraftment of Wsh mice with WT but not Mcpt4(-/-) mast cells restored intestinal epithelial cell migration, morphology, and intestinal epithelial barrier function. Collectively, these findings identify a mechanism by which mast cells regulate homeostatic intestinal epithelial migration and barrier function.
摘要
肠道屏障功能的改变被认为是肠道疾病（包括炎症性肠病和食物过敏）的一个主要诱发因素。然而，维持肠道屏障完整性的内在机制仍未被阐明。在这项研究中，我们证明了缺乏肥大细胞（Kit(W-sh/W-sh) [Wsh]）或肥大细胞糜酶（Mcpt4(-/-)）的小鼠与野生型（WT）小鼠相比，其基础小肠通透性显著降低。肠道屏障功能的改变与沿绒毛/隐窝轴的肠道上皮细胞迁移减少、肠道形态改变以及紧密连接蛋白-3 在隐窝中的表达失调有关。值得注意的是，将 Wsh 小鼠的肥大细胞移植为 WT 而不是 Mcpt4(-/-)的肥大细胞，可恢复肠道上皮细胞的迁移、形态和肠道上皮屏障功能。总的来说，这些发现确定了肥大细胞调节肠道上皮细胞稳态迁移和屏障功能的一种机制。
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