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Publication : Dynamic migration of γδ intraepithelial lymphocytes requires occludin.

First Author  Edelblum KL Year  2012
Journal  Proc Natl Acad Sci U S A Volume  109
Issue  18 Pages  7097-102
PubMed ID  22511722 Mgi Jnum  J:183907
Mgi Id  MGI:5319550 Doi  10.1073/pnas.1112519109
Citation  Edelblum KL, et al. (2012) Dynamic migration of gammadelta intraepithelial lymphocytes requires occludin. Proc Natl Acad Sci U S A 109(18):7097-102
abstractText  gammadelta intraepithelial lymphocytes (IELs) are located beneath or between adjacent intestinal epithelial cells and are thought to contribute to homeostasis and disease pathogenesis. Using in vivo microscopy to image jejunal mucosa of GFP gammadelta T-cell transgenic mice, we discovered that gammadelta IELs migrate actively within the intraepithelial compartment and into the lamina propria. As a result, each gammadelta IEL contacts multiple epithelial cells. Occludin is concentrated at sites of gammadelta IEL/epithelial interaction, where it forms a ring surrounding the gammadelta IEL. In vitro analyses showed that occludin is expressed by epithelial and gammadelta T cells and that occludin derived from both cell types contributes to these rings and to gammadelta IEL migration within epithelial monolayers. In vivo TNF administration, which results in epithelial occludin endocytosis, reduces gammadelta IEL migration. Further in vivo analyses demonstrated that occludin KO gammadelta T cells are defective in both initial accumulation and migration within the intraepithelial compartment. These data challenge the paradigm that gammadelta IELs are stationary in the intestinal epithelium and demonstrate that gammadelta IELs migrate dynamically to make extensive contacts with epithelial cells. The identification of occludin as an essential factor in gammadelta IEL migration provides insight into the molecular regulation of gammadelta IEL/epithelial interactions.
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