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Dynamic migration of ?? intraepithelial lymphocytes requires occludin.

ABSTRACT: ?? 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 ?? T-cell transgenic mice, we discovered that ?? IELs migrate actively within the intraepithelial compartment and into the lamina propria. As a result, each ?? IEL contacts multiple epithelial cells. Occludin is concentrated at sites of ?? IEL/epithelial interaction, where it forms a ring surrounding the ?? IEL. In vitro analyses showed that occludin is expressed by epithelial and ?? T cells and that occludin derived from both cell types contributes to these rings and to ?? IEL migration within epithelial monolayers. In vivo TNF administration, which results in epithelial occludin endocytosis, reduces ?? IEL migration. Further in vivo analyses demonstrated that occludin KO ?? T cells are defective in both initial accumulation and migration within the intraepithelial compartment. These data challenge the paradigm that ?? IELs are stationary in the intestinal epithelium and demonstrate that ?? IELs migrate dynamically to make extensive contacts with epithelial cells. The identification of occludin as an essential factor in ?? IEL migration provides insight into the molecular regulation of ?? IEL/epithelial interactions.

SUBMITTER: Edelblum KL

PROVIDER: S-EPMC3345021 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Dynamic migration of γδ intraepithelial lymphocytes requires occludin.

Edelblum Karen L KL Shen Le L Weber Christopher R CR Marchiando Amanda M AM Clay Bryan S BS Wang Yingmin Y Prinz Immo I Malissen Bernard B Sperling Anne I AI Turner Jerrold R JR

Proceedings of the National Academy of Sciences of the United States of America 20120417 18

γδ 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 γδ T-cell transgenic mice, we discovered that γδ IELs migrate actively within the intraepithelial compartment and into the lamina propria. As a result, each γδ IEL contacts multiple epithelial cells. Occludin is concentrated at sites of γδ IEL/epithelial interaction, ...[more]

PMID: 22511722

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Project description:Intraepithelial T lymphocytes (T-IELs), which constitute over 50% of the total T lymphocytes in the animal, patrol the mucosal epithelial lining to defend against pathogen invasion while maintaining gut homeostasis. In addition to expressing T cell markers such as CD4 and CD8, T-IELs display T cell receptors (TCR), including either TCRαβ or TCRγδ. Both humans and mice share similar T-IEL subsets: TCRγδ+, TCRαβ+CD8αα+, TCRαβ+CD4+, and TCRαβ+CD8αβ+. Among these subsets, human T-IELs are predominantly TCRαβ+ (over 80%), whereas those in mice are mostly TCRγδ+ (~60%). Of note, the majority of the TCRγδ+ subset expresses CD8αα in both species. Although T-IELs have been extensively studied in humans and mice, their profiles in cattle have not been well examined. Our study is the first to characterize bovine T-IELs using flow cytometry, where we identified several distinct features. The percentage of TCRγδ+ was comparable to that of TCRαβ+ T-IELs (both ~50% of CD3+), and the majority of bovine TCRγδ+ T-IELs did not express CD8 (CD8-) (above 60%). Furthermore, about 20% of TCRαβ+ T-IELs were CD4+CD8αβ+, and the remaining TCRαβ+ T-IELs were evenly distributed between CD4+ and CD8αβ+ (~40% of TCRαβ+ T-IELs each) with no TCRαβ+CD8αα+ identified. Despite these unique properties, bovine T-IELs, similar to those in humans and mice, expressed a high level of CD69, an activation and tissue-retention marker, and a low level of CD62L, a lymphoid adhesion marker. Moreover, bovine T-IELs produced low levels of inflammatory cytokines such as IFNγ and IL17A, and secreted small amounts of the immune regulatory cytokine TGFβ1. Hence, bovine T-IELs' composition largely differs from that of human and mouse, with the dominance of the CD8- population among TCRγδ+ T-IELs, the substantial presence of TCRαβ+CD4+CD8αβ+ cells, and the absence of TCRαβ+CD8αα+ T-IELs. These results provide the groundwork for conducting future studies to examine how bovine T-IELs respond to intestinal pathogens and maintain the integrity of the gut epithelial barrier in animals.

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Dynamic migration of ?? intraepithelial lymphocytes requires occludin.

Publications

Dynamic migration of γδ intraepithelial lymphocytes requires occludin.

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