Alteration of intestinal epithelial function by intraepithelial lymphocyte homing

Shibahara, Takeshi; Miyazaki, Kunihiko; Sato, Daisuke; Matsui, Hirohumi; Yanaka, Akinori; Nakahara, Akira; Tanaka, Naomi

doi:10.1007/s00535-005-1631-y

Cited by 20 publications

(12 citation statements)

References 35 publications

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“…[61][62][63] In addition to upregulating adhesion molecules in epithelial cells, IELs enhance chemokine and cytokine production and eliminate senescent epithelial cells, thereby ensuring rapid epithelial regeneration, which in turn helps maintain the functional integrity of the mucosal barrier. [64][65][66] In CD, lesion-specific T-cell clones were found in aphthoid ulcers, in addition to there being specific clonal expansion of T-cell receptor at the epithelial ulcers. 67 This suggests that specific lymphocytes contribute to epithelial inflammatory pathogenesis.…”

Section: Subepithelial Immune Cells In Maintaining Mucosal Intestinalmentioning

confidence: 98%

Importance of disrupted intestinal barrier in inflammatory bowel diseases

Salim

Söderholm

2011

Inflammatory Bowel Diseases

505

342

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The current paradigm of inflammatory bowel diseases (IBD), both Crohn's disease (CD) and ulcerative colitis (UC), involves the interaction between environmental factors in the intestinal lumen and inappropriate host immune responses in genetically predisposed individuals. The intestinal mucosal barrier has evolved to maintain a delicate balance between absorbing essential nutrients while preventing the entry and responding to harmful contents. In IBD, disruptions of essential elements of the intestinal barrier lead to permeability defects. These barrier defects exacerbate the underlying immune system, subsequently resulting in tissue damage. The epithelial phenotype in active IBD is very similar in CD and UC. It is characterized by increased secretion of chloride and water, leading to diarrhea, increased permeability via both the transcellular and paracellular routes, and increased apoptosis of epithelial cells. The main cytokine that seems to drive these changes is tumor necrosis factor alpha in CD, whereas interleukin (IL)-13 may be more important in UC. Therapeutic restoration of the mucosal barrier would provide protection and prevent antigenic overload due to intestinal "leakiness." Here we give an overview of the key players of the intestinal mucosal barrier and review the current literature from studies in humans and human systems on mechanisms underlying mucosal barrier dysfunction in IBD.

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Section: Subepithelial Immune Cells In Maintaining Mucosal Intestinalmentioning

confidence: 98%

Importance of disrupted intestinal barrier in inflammatory bowel diseases

Salim

Söderholm

2011

Inflammatory Bowel Diseases

505

342

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“…This was associated with an increase in TGF‐β and a decrease in IFN‐γ (Inagaki‐Ohara et al ., 2004). Furthermore, γδ T cells have been shown to decrease IL‐15 secretion by IECs and increase IL‐8 and IFN‐γ, all of which have been associated with restoring epithelial homeostasis (Shibahara et al ., 2005). Through their role in maintaining tissue integrity and modulating inflammatory responses, γδ T cells act as a special type of innate T cell that is important in gut homeostasis.…”

Section: Epitheliummentioning

confidence: 99%

Control of mucosal polymicrobial populations by innate immunity

Mason

Huffnagle

2009

Cellular Microbiology

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SummaryThe gastrointestinal tract carries out the complex process of localizing the polymicrobial populations of the indigenous microbiota to the lumenal side of the GI mucosa while absorbing nutrients from the lumen and preventing damage to the mucosa. This process is accomplished through a combination of physical, innate and adaptive host defences and a 'strategic alliance' with members of the microbiota. To cope with the constant exposure to a diverse microbial community, the GI tract, through the actions of a number of specialized cells in the epithelium and lamina propria, has layers of humoral, physical and cellular defences that limit attachment, invasion and dissemination of the indigenous microbiota. However, the role of the microbiota in this dynamic balance is vital and serves as another level of 'innate' defence. We are just beginning to understand how bacterial metabolites aid in the control of potential pathogens within the microbiota and limit inflammatory responses to the microbiota, concepts that will impact our understanding of the biological effects of antibiotics, diet and probiotics on mucosal inflammatory responses.

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“…Indeed CCR9 is required for effector CD4+ T lymphocyte entry into small intestinal lamina propria [17]. Under inflammatory conditions intra-epithelial lymphocytes alter barrier function, consequently enhancing intestinal permeability and further enhancing chemokine production [18]. In particular, IFABP and IBAP were inversely correlated with gastric emptying, indicating small bowel immune activation with intestinal barrier alterations associated with gastric emptying.…”

Section: Discussionmentioning

confidence: 99%

Intestinal T lymphocyte homing is associated with gastric emptying and epithelial barrier function in critically ill: a prospective observational study

et al. 2017

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BackgroundImpaired gastric emptying is common in critically ill patients. Intestinal dysmotility, a major cause of feed intolerance, may foster infectious complications due to mucosal barrier disruption. However, little is known about gut-directed immune activation, intestinal barrier function and its association with impaired gastric emptying in critically ill patients at ICU admission.MethodsWe conducted a prospective observational study at two tertiary care medical ICUs. Fifty consecutive patients needing invasive mechanical ventilation were recruited within 24 h of ICU admission, prior to any nutritional support. The acute physiology and chronic health evaluation (APACHE) II score, the sequential organ failure assessment (SOFA) score and the multiple organ dysfunction score (MODS) were used to assess illness severity and multiple organ dysfunction. Gastric emptying was assessed by paracetamol absorption test. Peripheral blood mononuclear cells were freshly isolated and cultured for 24 h, and TNF-α, IL-1β and IL-10 measured in cell culture supernatants and in serum by ELISA. The intestinal epithelial barrier was assessed, quantifying serum concentrations of intestinal fatty acid binding protein (I-FABP), ileal bile-acid binding protein (I-BABP) and zonulin-1 by ELISA. Small bowel homing T lymphocytes (CD4+ α4β7 + CCR9+) were analyzed by flow cytometry. The Mann-Whitney test and Spearman correlation were used in statistical evaluation.ResultsCD4 + α4β7 + CCR9+ T lymphocytes were inversely correlated with gastric emptying. Patients with delayed gastric emptying at ICU admission (n = 35) had significantly higher serum and PBMC-induced TNF-α and IL-1β and increased intestinal barrier disruption reflected by higher I-FABP, I-BABP and zonulin-1. Patients who died in the ICU had significantly impaired gastric empting at admission compared to ICU survivors. No differences were observed in APACHE II, SOFA or MODS in patients with delayed gastric emptying compared to patients with normal gastric emptying.ConclusionsExaggerated CD4 + α4β7 + CCR9+ T lymphocyte homing with increased pro-inflammatory cytokine release and intestinal epithelial barrier disruption are associated with delayed gastric emptying. This is not simply due to differences in overall severity of illness at ICU admission and may represent a pathophysiological mechanism of gut-directed immune activation leading to impaired barrier function in the critically ill.

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Alteration of intestinal epithelial function by intraepithelial lymphocyte homing

Cited by 20 publications

References 35 publications

Importance of disrupted intestinal barrier in inflammatory bowel diseases

Importance of disrupted intestinal barrier in inflammatory bowel diseases

Control of mucosal polymicrobial populations by innate immunity

Intestinal T lymphocyte homing is associated with gastric emptying and epithelial barrier function in critically ill: a prospective observational study

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