Dynamic migration of γδ intraepithelial lymphocytes requires occludin
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Dynamic migration of γδ intraepithelial lymphocytes requires occludin. / Edelblum, Karen L; Shen, Le; Weber, Christopher R; Marchiando, Amanda M; Clay, Bryan S; Wang, Yingmin; Prinz, Immo; Malissen, Bernard; Sperling, Anne I; Turner, Jerrold R.
In: P NATL ACAD SCI USA, Vol. 109, No. 18, 01.05.2012, p. 7097-102.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Dynamic migration of γδ intraepithelial lymphocytes requires occludin
AU - Edelblum, Karen L
AU - Shen, Le
AU - Weber, Christopher R
AU - Marchiando, Amanda M
AU - Clay, Bryan S
AU - Wang, Yingmin
AU - Prinz, Immo
AU - Malissen, Bernard
AU - Sperling, Anne I
AU - Turner, Jerrold R
PY - 2012/5/1
Y1 - 2012/5/1
N2 - 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, where it forms a ring surrounding the γδ IEL. In vitro analyses showed that occludin is expressed by epithelial and γδ T cells and that occludin derived from both cell types contributes to these rings and to γδ IEL migration within epithelial monolayers. In vivo TNF administration, which results in epithelial occludin endocytosis, reduces γδ IEL migration. Further in vivo analyses demonstrated that occludin KO γδ T cells are defective in both initial accumulation and migration within the intraepithelial compartment. These data challenge the paradigm that γδ IELs are stationary in the intestinal epithelium and demonstrate that γδ IELs migrate dynamically to make extensive contacts with epithelial cells. The identification of occludin as an essential factor in γδ IEL migration provides insight into the molecular regulation of γδ IEL/epithelial interactions.
AB - 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, where it forms a ring surrounding the γδ IEL. In vitro analyses showed that occludin is expressed by epithelial and γδ T cells and that occludin derived from both cell types contributes to these rings and to γδ IEL migration within epithelial monolayers. In vivo TNF administration, which results in epithelial occludin endocytosis, reduces γδ IEL migration. Further in vivo analyses demonstrated that occludin KO γδ T cells are defective in both initial accumulation and migration within the intraepithelial compartment. These data challenge the paradigm that γδ IELs are stationary in the intestinal epithelium and demonstrate that γδ IELs migrate dynamically to make extensive contacts with epithelial cells. The identification of occludin as an essential factor in γδ IEL migration provides insight into the molecular regulation of γδ IEL/epithelial interactions.
KW - Animals
KW - Cell Movement/immunology
KW - Gene Knockdown Techniques
KW - Green Fluorescent Proteins/genetics
KW - Intestinal Mucosa/cytology
KW - Membrane Proteins/antagonists & inhibitors
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Mice, Transgenic
KW - Occludin
KW - Phosphoproteins/antagonists & inhibitors
KW - Receptors, Antigen, T-Cell, gamma-delta/metabolism
KW - T-Lymphocyte Subsets/immunology
KW - Zonula Occludens-1 Protein
U2 - 10.1073/pnas.1112519109
DO - 10.1073/pnas.1112519109
M3 - SCORING: Journal article
C2 - 22511722
VL - 109
SP - 7097
EP - 7102
JO - P NATL ACAD SCI USA
JF - P NATL ACAD SCI USA
SN - 0027-8424
IS - 18
ER -