Differentiating Between Tight Junction-Dependent and Tight Junction-Independent Intestinal Barrier Loss In Vivo

Chánez-Paredes, Sandra; Abtahi, Shabnam; Kuo, Wei-Ting; Turner, Jerrold R.

doi:10.1007/7651_2021_389

Cited by 28 publications

(35 citation statements)

References 61 publications

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“…Although 4-kDa dextran permeability increases were markedly greater in DSStreated ZO-1 KO.IEC mice relative to WT mice, this was due to flux across the unrestricted, rather than leak, pathway, because serum recovery of 70-kDa dextran was also far greater in ZO-1 KO.IEC , relative to WT, mice (Figure 3G), and both dextrans are able to traverse the unrestricted pathway (Figure 2E). 14 This contrasts with the specific leak pathway up-regulation indicated by the increased flux of 4-kDa, not 70-kDa, dextran in unstressed ZO-1 KO.IEC mice (Figure 2E). As with 1% DSS, 2% DSS failed to induce increases in DNA synthesis (Figure 3H) or the MKI67 (Ki-67) proliferative index (Figure 3I) in ZO-1 KO.IEC mice.…”

Section: Intestinal Epithelial Zo-1 Is Critical For Efficient Mucosal...mentioning

confidence: 69%

“…We next assessed in vivo intestinal barrier function of ZO-1 KO.IEC mice. We focused on leak and unrestricted pathway permeabilities using 4-kDa dextran (28-Å diameter) and 70-kDa dextran (120-Å diameter), respectively, 13,14 because ZO-1 knockdown increases leak pathway permeability in vitro. 15 Flux of 4-kDa dextran, but not 70-kDa dextran, was mildly increased in ZO-1 KO.IEC mice (Figure 2E), consistent with increased leak pathway, that is macromolecular, permeability in vivo.…”

Section: Limitationsmentioning

confidence: 99%

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The Tight Junction Protein ZO-1 Is Dispensable for Barrier Function but Critical for Effective Mucosal Repair

et al. 2021

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Section: Intestinal Epithelial Zo-1 Is Critical For Efficient Mucosal...mentioning

confidence: 69%

Section: Limitationsmentioning

confidence: 99%

The Tight Junction Protein ZO-1 Is Dispensable for Barrier Function but Critical for Effective Mucosal Repair

et al. 2021

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“…Hence, IEB integrity is associated with a broad range of diseases including inflammatory bowel disease (IBD), irritable bowel syndrome, and even Celiac disease ( 54 – 56 ). A complete loss of Zbtb20 expression in T cells resulted in a measurable increase of the unrestricted pathway, which is distinct from both the paracellular and transcellular pathways that have charge and size selectivity ( 57 ) and directly indicated IEB damage in young (8-week-old), otherwise healthy mice. Therefore, it is tempting to speculate that reduced activity or frequency of Zbtb20 + T regs might be associated with cumulative IEB damage over time leading to a predisposition for the diseases like those mentioned above.…”

Section: Discussionmentioning

confidence: 99%

Zbtb20 identifies and controls a thymus-derived population of regulatory T cells that play a role in intestinal homeostasis

et al. 2022

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The expression of BTB-ZF transcription factors such as ThPOK in CD4 + T cells, Bcl6 in T follicular helper cells, and PLZF in natural killer T cells defines the fundamental nature and characteristics of these cells. Screening for lineage-defining BTB-ZF genes led to the discovery of a subset of T cells that expressed Zbtb20. About half of Zbtb20 + T cells expressed FoxP3, the lineage-defining transcription factor for regulatory T cells (T regs ). Zbtb20 + T regs were phenotypically and genetically distinct from the larger conventional T reg population. Zbtb20 + T regs constitutively expressed mRNA for interleukin-10 and produced high levels of the cytokine upon primary activation. Zbtb20 + T regs were enriched in the intestine and specifically expanded when inflammation was induced by the use of dextran sodium sulfate. Conditional deletion of Zbtb20 in T cells resulted in a loss of intestinal epithelial barrier integrity. Consequently, knockout (KO) mice were acutely sensitive to colitis and often died because of the disease. Adoptive transfer of Zbtb20 + T regs protected the Zbtb20 conditional KO mice from severe colitis and death, whereas non-Zbtb20 T regs did not. Zbtb20 was detected in CD24 hi double-positive and CD62L lo CD4 single-positive thymocytes, suggesting that expression of the transcription factor and the phenotype of these cells were induced during thymic development. However, Zbtb20 expression was not induced in “conventional” T regs by activation in vitro or in vivo. Thus, Zbtb20 expression identified and controlled the function of a distinct subset of T regs that are involved in intestinal homeostasis.

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“…Certain proteins have been found to have other properties; junctional adhesion molecule A is also considered to be responsible for leukocyte migration ( 24 , 25 ). Mucosal damage, such as in ulcers of patients with inflammatory bowel disease (IBD), disrupts this complex regulatory structure and causes an uncontrolled leakage through the barrier ( 26 – 28 ) ( Figure 1 ).…”

Section: Intestinal Permeability and The Microbiomementioning

confidence: 99%

The Influence of Nutrition on Intestinal Permeability and the Microbiome in Health and Disease

et al. 2022

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The leakage of the intestinal barrier and the disruption of the gut microbiome are increasingly recognized as key factors in different pathophysiological conditions, such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), chronic liver diseases, obesity, diabetes mellitus, types of cancer, and neuropsychiatric disorders. In this study, the mechanisms leading to dysbiosis and “leaky gut” are reviewed, and a short summary of the current knowledge regarding different diseases is provided. The simplest way to restore intestinal permeability and the microbiota could be ideal nutrition. Further therapeutic options are also available, such as the administration of probiotics or postbiotics or fecal microbiota transplantation.

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Differentiating Between Tight Junction-Dependent and Tight Junction-Independent Intestinal Barrier Loss In Vivo

Cited by 28 publications

References 61 publications

The Tight Junction Protein ZO-1 Is Dispensable for Barrier Function but Critical for Effective Mucosal Repair

The Tight Junction Protein ZO-1 Is Dispensable for Barrier Function but Critical for Effective Mucosal Repair

Zbtb20 identifies and controls a thymus-derived population of regulatory T cells that play a role in intestinal homeostasis

The Influence of Nutrition on Intestinal Permeability and the Microbiome in Health and Disease

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