Mast cells regulate homeostatic intestinal epithelial migration and barrier function by a chymase/Mcpt4-dependent mechanism

被引：146

作者：

Groschwitz, Katherine R. ^{[1
,2
]}

Ahrens, Richard ^{[1
]}

Osterfeld, Heather ^{[1
]}

Gurish, Michael F. ^{[4
]}

Han, Xiaonan ^{[3
]}

Abrink, Magnus ^{[5
]}

Finkelman, Fred D. ^{[2
]}

Pejler, Gunnar ^{[6
]}

Hogan, Simon P. ^{[1
]}

机构：

[1] Univ Cincinnati, Cincinnati Childrens Hosp, Med Ctr, Coll Med,Div Allergy & Immunol, Cincinnati, OH 45229 USA

[2] Univ Cincinnati, Cincinnati Childrens Hosp, Med Ctr, Coll Med,Div Immunobiol, Cincinnati, OH 45229 USA

[3] Univ Cincinnati, Cincinnati Childrens Hosp, Div Gastroenterol Nutr & Hepatol, Dept Pediat,Med Ctr,Coll Med, Cincinnati, OH 45229 USA

[4] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

[5] Uppsala Univ, Dept Med Biochem & Microbiol, SE-75105 Uppsala, Sweden

[6] Swedish Univ Agr Sci, Dept Mol Biosci, S-75007 Uppsala, Sweden

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2009年 / 106卷 / 52期

基金：

美国国家卫生研究院;

关键词：

homeostasis; intestinal permeability; mast cell protease-4; CROHNS-DISEASE; TRICHINELLA-SPIRALIS; NEMATODE INFECTION; ION-TRANSPORT; UP-REGULATION; PERMEABILITY; CHYMASE; PROTEASES; MOUSE; MICE;

D O I：

10.1073/pnas.0906372106

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：22381 / 22386

页数：6

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