Intestinal Intraepithelial Lymphocytes Sustain the Epithelial Barrier Function against<i>Eimeria vermiformis</i>Infection

Inagaki–Ohara, Kyoko; Dewi, Fitriya N.; Hisaeda, Hajime; Smith, Adrian L.; Jimi, Fumiko; Miyahira, Maki; Farid, Ayman Samir; Horii, Yoichiro; Nawa, Yukifumi

doi:10.1128/iai.02024-05

Cited by 85 publications

(60 citation statements)

References 49 publications

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“…γδ IELs are involved in the regulation of the mucosal microenvironment in response to intestinal disease, including inflammatory bowel disease (44), celiac disease, graft-vs.-host disease (45), and parasite infection (14,15). However, the precise role of γδ IELs remains controversial.…”

Section: Discussionmentioning

confidence: 99%

“…Our data demonstrating the ability of γδ IELs to migrate and contact multiple epithelial cells over a short time provide a potential mechanism by which γδ IELs, which are greatly outnumbered by epithelial cells, can impact the entire epithelium. This migration can also be considered a form of surveillance that regulates intracellular signaling in both by γδ IELs and epithelial cells to prevent epithelial injury and infection (12)(13)(14)(15). The acceleration of γδ T-cell migration within the peri-BM and lamina propria compartments after TNF treatment may therefore represent a form of innate immune activation (Table 1).…”

Section: Discussionmentioning

confidence: 99%

“…Although the majority of these IELs express the γδ T cell receptor, and epidermal γδ IELs have been studied extensively (1)(2)(3)(4), the functions of intestinal γδ IELs remain poorly understood. Some studies have shown that γδ IELs contribute to progression of immune-mediated colitis (5)(6)(7); other data suggest that γδ IELs contribute to mucosal homeostasis (8,9) by secreting keratinocyte growth factor (10,11) and antimicrobial peptides (12,13), suppressing CD4 + T-cell expansion through TGF-β and IL-10 production (8,9) and promoting barrier maintenance via poorly understood mechanisms (13)(14)(15). These observations and the small number of IELs relative to intestinal epithelial cells are difficult to reconcile with the widely held belief that γδ IELs have limited motility (1,16).…”

mentioning

confidence: 99%

“…To elucidate the mechanism by which γδ IELs migrate into the epithelium, we investigated potential mediators of γδ IEL/epithelial interactions. Several reports indicate that IELs express junction-associated proteins, including occludin, junctional adhesion molecule-A, ZO-1, β-catenin, and the E-cadherin ligand CD103 (14,15,18,22). Immunostaining showed that γδ, but not αβ, IELs express ZO-1 and occludin (Fig.…”

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confidence: 99%

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Dynamic migration of γδ intraepithelial lymphocytes requires occludin

Edelblum¹,

Shen²,

Weber³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

146

180

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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.intestine | tight junction T he intestine is one of the few peripheral tissues to contain a large population of intraepithelial lymphocytes (IELs), with one IEL for every 5-10 epithelial cells. Although the majority of these IELs express the γδ T cell receptor, and epidermal γδ IELs have been studied extensively (1-4), the functions of intestinal γδ IELs remain poorly understood. Some studies have shown that γδ IELs contribute to progression of immune-mediated colitis (5-7); other data suggest that γδ IELs contribute to mucosal homeostasis (8, 9) by secreting keratinocyte growth factor (10, 11) and antimicrobial peptides (12, 13), suppressing CD4 + T-cell expansion through TGF-β and IL-10 production (8, 9) and promoting barrier maintenance via poorly understood mechanisms (13-15). These observations and the small number of IELs relative to intestinal epithelial cells are difficult to reconcile with the widely held belief that γδ IELs have limited motility (1, 16).Further understanding of γδ IEL function will require definition of the molecular structures that regulate interactions between intestinal epithelial and γδ T cells. On the basis of the location of epithelial/γδ IEL contact sites along epithelial lateral membranes, it is likely that epithelial proteins targeted to these domains, including apical junction complex components, are involved in these interactions. Attractive candidates include E-cadherin, which can bind CD103 (α E β 7 integrin) expressed by IELs (17), as well as tight junction proteins. For example, γδ IELs express several epithelial tight junction proteins, including occludin and zonula occludens-1 (ZO-1) (18), that may bind directly or indirectly t...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Dynamic migration of γδ intraepithelial lymphocytes requires occludin

Edelblum¹,

Shen²,

Weber³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

146

180

View full text Add to dashboard Cite

show abstract

“…These cells play a vital role in host defence at the mucosal surface and facilitate maintenance of a competent intestinal barrier. For example, they have been shown to modulate expression of tight cell junction proteins by epithelial cells in order to maintain barrier integrity following infection (Dalton et al, 2006;Inagaki-Ohara et al, 2006). Furthermore, they regulate proliferation and differentiation of epithelial cells and play a role in induction of apoptosis in senescent or infected cells, allowing for rapid regeneration and reducing the risk of leaks (Guy-Grand et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Streptococcus thermophilus NCIMB 41856 ameliorates signs of colitis in an animal model of inflammatory bowel disease

Bailey

Vince²,

Williams³

et al. 2017

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Treatment of inflammatory bowel disease (IBD) is mainly based on suppression of symptoms, often with numerous side effects. Trials of probiotics in IBD have frequently produced disappointing results. The majority of probiotics are unusual, since they do not require iron for growth, unlike many bacteria resident in the intestine. The IBD intestine is iron-rich due to bleeding and use of oral iron supplements; conventional probiotics would be rapidly outcompeted. We have evaluated an iron-responsive Streptococcus thermophilus strain for its potential to reduce signs of colitis. Efficacy of S. thermophilus was evaluated in the dextran sodium sulphate mouse model of colitis. Treated animals were given 1×108 cfu S. thermophilus per day and clinical observations were taken daily. At termination, gross and histopathological signs of disease, cellular infiltration, location of bacteria, and cytokine expression in the intestine were determined. S. thermophilus delayed onset of colitis and reduced clinical signs of disease, including bodyweight loss and gastrointestinal bleeding. It reduced bacterial translocation into the colonic tissue. Increased numbers of CD8+ intraepithelial lymphocytes were seen in control animals treated with S. thermophilus. S. thermophilus had no effect on gross pathology, histopathology or cytokine production in either colitic or control animals. We propose that S. thermophilus promotes maintenance of mucosal barrier function which reduces bacterial translocation, thereby reducing immune stimulation and associated inflammation. This allows mucosal healing, reducing gastrointestinal bleeding and weight loss. This could be studied as a locally-acting adjunct or alternative to current IBD treatments.

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Electrolyte Secretion and Absorption in the Small Intestine and Colon

Barrett

Keely

2015

Yamada' S Textbook of Gastroenterology

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Intestinal Intraepithelial Lymphocytes Sustain the Epithelial Barrier Function againstEimeria vermiformisInfection

Cited by 85 publications

References 49 publications

Dynamic migration of γδ intraepithelial lymphocytes requires occludin

Dynamic migration of γδ intraepithelial lymphocytes requires occludin

Streptococcus thermophilus NCIMB 41856 ameliorates signs of colitis in an animal model of inflammatory bowel disease

Electrolyte Secretion and Absorption in the Small Intestine and Colon

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