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Research article2009Peer reviewedOpen access

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

Groschwitz, Katherine R.; Ahrens, Richard; Osterfeld, Heather; Gurish, Michael F.; Han, Xiaonan; Abrink, Magnus; Finkelman, Fred D.; Pejler, Gunnar; Hogan, Simon P.


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.


homeostasis; intestinal permeability; mast cell protease-4

Published in

Proceedings of the National Academy of Sciences
2009, Volume: 106, number: 52, pages: 22381-22386

        SLU Authors

      • Pejler, Gunnar

        • Department of Molecular Biosciences, Swedish University of Agricultural Sciences

      UKÄ Subject classification

      Cell Biology

      Publication identifier


      Permanent link to this page (URI)