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. |