The Role of Intestinal Epithelial Cells and Their Cellular Interactions

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: 31 March 2025 | Viewed by 6917

Special Issue Editor


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Guest Editor
Department of Animal and Avian Sciences, University of Maryland, College Park, MD, USA
Interests: mucosal barrier, tight and adherens junctions, intestinal stem cells, mesenchymal stromal cells, and postnatal intestinal development

Special Issue Information

Dear Colleagues,

This Special Issue, “The Role of Intestinal Epithelial Cells and their Cellular Interactions”, will mainly focus on the role of intestinal epithelial cells (IECs) and their regulation and crosstalk with stromal and immune cells.

The intestinal mucosal barrier represents the largest interface between the luminal contents and the body's internal milieu. Single-layered IECs are a semipermeable barrier that allows the absorption of nutrients and transport of substances and prevents the entry of harmful substances, luminal antigens, and pathogens. Due to the harsh luminal environment, IECs possess a great capacity for self-renewal to maintain organ homeostasis and promote regeneration, which is fueled by a population of intestinal stem cells. The IECs dynamically interact with both intestinal stromal and immune cells to maintain tissue homeostasis and alterations to pathological conditions. Understanding the impact of IECs and their interaction with subepithelial cells is essential for improving gut health.

We cordially invite authors to submit original research or review articles pertaining to this important and fast-progressing field of biomedicine. Potential topics include, but are not limited to:

 

  • The mucosal barrier in gastrointestinal physiology and pathology;
  • Intestinal stem cell biology in tissue homeostasis and regeneration;
  • The crosstalk of intestinal epithelial cells with stromal or immune cells.

Dr. Younggeon Jin
Guest Editor

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Keywords

  • intestinal epithelial barrier
  • tight junctions
  • intestinal stem cells
  • mesenchymal stromal cells
  • immune cells

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Published Papers (6 papers)

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Research

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16 pages, 3981 KiB  
Article
Integration of Stromal Cells and Hydrogel Below Epithelium Results in Optimal Barrier Properties of Small Intestine Organoid Models
by Melis Asal, Maria Thon, Taco Waaijman, Hetty J. Bontkes, Sandra J. van Vliet, Reina E. Mebius and Susan Gibbs
Biomedicines 2024, 12(12), 2913; https://doi.org/10.3390/biomedicines12122913 (registering DOI) - 21 Dec 2024
Viewed by 272
Abstract
Background/Objectives: The barrier properties of the human small intestine play a crucial role in regulating digestion, nutrient absorption and drug metabolism. Current in vitro organotypic models consist only of an epithelium, which does not take into account the possible role of stromal [...] Read more.
Background/Objectives: The barrier properties of the human small intestine play a crucial role in regulating digestion, nutrient absorption and drug metabolism. Current in vitro organotypic models consist only of an epithelium, which does not take into account the possible role of stromal cells such as fibroblasts or the extracellular matrix (ECM) which could contribute to epithelial barrier properties. Therefore, the aim of this study was to determine whether these stromal cells or ECM were beneficial or detrimental to barrier function when incorporated into an organotypic human small intestine model. Methods: Intestinal epithelial cell lines or primary cell organoids derived from the epithelial stem cells of the small intestine were cultivated either on a porous Transwell membrane (epithelial model) or on a primary small intestinal stromal cell-populated collagen-fibrin hydrogel (full thickness model). Results: Both models expressed villin (enterocytes), lysozyme (Paneth cells), Ki67 (proliferative cells) and zonula occludens-1 (tight junctions). The polarized epithelial barriers of the full thickness models demonstrated a significant decrease in transepithelial electrical resistance (TEER) with values comparable to that found in the native small intestine in contrast to the higher TEER values observed in the epithelial models. This correlated to an increase in secreted zonulin, a regulator of intestine permeability, in the full thickness models. The decreased TEER values were due to both the stromal cells and the choice of the hydrogel versus the Transwell membrane. Moreover, erythropoietin and epithelial growth factor secretion, which have roles in regulating barrier integrity, directly correlated with the changes in TEER and permeability. Conclusions: This study emphasizes the importance of different cell types being incorporated into small intestine models and, also, the influence of the scaffold or matrix used. Full article
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12 pages, 1222 KiB  
Article
Hyperosmotic Stress Induces the Expression of Organic Osmolyte Transporters in Porcine Intestinal Cells and Betaine Exerts a Protective Effect on the Barrier Function
by Elena De Angelis, Paolo Borghetti, Benedetta Passeri, Valeria Cavalli, Luca Ferrari, Melania Andrani, Paolo Martelli and Roberta Saleri
Biomedicines 2024, 12(10), 2391; https://doi.org/10.3390/biomedicines12102391 - 18 Oct 2024
Viewed by 790
Abstract
Background/objectives: The porcine intestinal epithelium plays a fundamental role as a defence interface against pathogens. Its alteration can cause severe inflammatory conditions and diseases. Hyperosmotic stress under physiological conditions and upon pathogen challenge can cause malabsorption. Different cell types counteract the osmolarity increase [...] Read more.
Background/objectives: The porcine intestinal epithelium plays a fundamental role as a defence interface against pathogens. Its alteration can cause severe inflammatory conditions and diseases. Hyperosmotic stress under physiological conditions and upon pathogen challenge can cause malabsorption. Different cell types counteract the osmolarity increase by accumulating organic osmolytes such as betaine, taurine, and myo-inositol through specific transporters. Betaine is known for protecting cells from hyperosmotic stress and has positive effects when fed to pigs. The aim of this study is to demonstrate the modulation of osmolyte transporters gene expression in IPEC-J2 during osmolarity changes and assess the effects of betaine. Methods: IPEC-J2 were seeded in transwells, where differentiate as a polarized monolayer. Epithelial cell integrity (TEER), oxidative stress (NO) and gene expression of osmolyte transporters, tight junction proteins (TJp) and pro-inflammatory cytokines were evaluated. Results: Cells treated with NaCl hyperosmolar medium (500 mOsm/L) showed a TEER decrease at 3 h and detachment within 24 h, associated with an osmolyte transporters reduction. IPEC-J2 treated with mannitol hyperosmolar medium (500 mOsm/L) upregulated taurine (TauT), myo-inositol (SMIT) and betaine (BGT1) transporters expression. A decrease in TJp expression was associated with a TEER decrease and an increase in TNFα, IL6, and IL8. Betaine could attenuate the hyperosmolarity-induced reduction in TEER and TJp expression, the NO increase and cytokines upregulation. Conclusions: This study demonstrates the expression of osmolyte transporters in IPEC-J2, which was upregulated upon hyperosmotic treatment. Betaine counteracts changes in intracellular osmolarity by contributing to maintaining the epithelial barrier function and reducing the inflammatory condition. Compatible osmolytes may provide beneficial effects in therapies for diseases characterized by inflammation and TJp-related dysfunctions. Full article
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Review

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20 pages, 1213 KiB  
Review
Overview of the Trending Enteric Viruses and Their Pathogenesis in Intestinal Epithelial Cell Infection
by Chi-Chong Chio, Jou-Chun Chien, Hio-Wai Chan and Hsing-I Huang
Biomedicines 2024, 12(12), 2773; https://doi.org/10.3390/biomedicines12122773 - 5 Dec 2024
Viewed by 1117
Abstract
Enteric virus infection is a major public health issue worldwide. Enteric viruses have become epidemic infectious diseases in several countries. Enteric viruses primarily infect the gastrointestinal tract and complete their life cycle in intestinal epithelial cells. These viruses are transmitted via the fecal–oral [...] Read more.
Enteric virus infection is a major public health issue worldwide. Enteric viruses have become epidemic infectious diseases in several countries. Enteric viruses primarily infect the gastrointestinal tract and complete their life cycle in intestinal epithelial cells. These viruses are transmitted via the fecal–oral route through contaminated food, water, or person to person and cause similar common symptoms, including vomiting, abdominal pain, and diarrhea. Diarrheal disease is the third leading cause of death in children under five years of age, accounting for approximately 1.7 billion cases and 443,832 deaths annually in this age group. Additionally, some enteric viruses can invade other tissues, leading to severe conditions and even death. The pathogenic mechanisms of enteric viruses are also unclear. In this review, we organized the research on trending enteric virus infections, including rotavirus, norovirus, adenovirus, Enterovirus-A71, Coxsackievirus A6, and Echovirus 11. Furthermore, we discuss the gastrointestinal effects and pathogenic mechanisms of SARS-CoV-2 in intestinal epithelial cells, given the gastrointestinal symptoms observed during the COVID-19 pandemic. We conducted a literature review on their pathogenic mechanisms, which serves as a guide for formulating future treatment strategies for enteric virus infections. Full article
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18 pages, 3903 KiB  
Review
Crosstalk Within the Intestinal Epithelium: Aspects of Intestinal Absorption, Homeostasis, and Immunity
by Liang-En Yu, Wen-Chin Yang and Yu-Chaun Liang
Biomedicines 2024, 12(12), 2771; https://doi.org/10.3390/biomedicines12122771 - 5 Dec 2024
Viewed by 567
Abstract
Gut health is crucial in many ways, such as in improving human health in general and enhancing production in agricultural animals. To maximize the effect of a healthy gastrointestinal tract (GIT), an understanding of the regulation of intestinal functions is needed. Proper intestinal [...] Read more.
Gut health is crucial in many ways, such as in improving human health in general and enhancing production in agricultural animals. To maximize the effect of a healthy gastrointestinal tract (GIT), an understanding of the regulation of intestinal functions is needed. Proper intestinal functions depend on the activity, composition, and behavior of intestinal epithelial cells (IECs). There are various types of IECs, including enterocytes, Paneth cells, enteroendocrine cells (EECs), goblet cells, tuft cells, M cells, and intestinal epithelial stem cells (IESCs), each with unique 3D structures and IEC distributions. Although the communication between IECs and other cell types, such as immune cells and neurons, has been intensively reviewed, communication between different IECs has rarely been addressed. The present paper overviews the networks among IECs that influence intestinal functions. Intestinal absorption is regulated by incretins derived from EECs that induce nutrient transporter activity in enterocytes. EECs, Paneth cells, tuft cells, and enterocytes release signals to activate Notch signaling, which modulates IESC activity and intestinal homeostasis, including proliferation and differentiation. Intestinal immunity can be altered via EECs, goblet cells, tuft cells, and cytokines derived from IECs. Finally, tools for investigating IEC communication have been discussed, including the novel 3D intestinal cell model utilizing enteroids that can be considered a powerful tool for IEC communication research. Overall, the importance of IEC communication, especially EECs and Paneth cells, which cover most intestinal functional regulating pathways, are overviewed in this paper. Such a compilation will be helpful in developing strategies for maintaining gut health. Full article
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19 pages, 1513 KiB  
Review
Subepithelial Stromal Cells: Their Roles and Interactions with Intestinal Epithelial Cells during Gut Mucosal Homeostasis and Regeneration
by Hammed Ayansola, Edith J. Mayorga and Younggeon Jin
Biomedicines 2024, 12(3), 668; https://doi.org/10.3390/biomedicines12030668 - 17 Mar 2024
Viewed by 1848
Abstract
Intestinal epithelial cell activities during homeostasis and regeneration are well described, but their potential interactions with stromal cells remain unresolved. Exploring the functions of these heterogeneous intestinal mesenchymal stromal cells (iMSCs) remains challenging. This difficulty is due to the lack of specific markers [...] Read more.
Intestinal epithelial cell activities during homeostasis and regeneration are well described, but their potential interactions with stromal cells remain unresolved. Exploring the functions of these heterogeneous intestinal mesenchymal stromal cells (iMSCs) remains challenging. This difficulty is due to the lack of specific markers for most functionally homogenous subpopulations. In recent years, however, novel clustering techniques such as single-cell RNA sequencing (scRNA-seq), fluorescence-activated cell sorting (FACS), confocal microscope, and computational remodeling of intestinal anatomy have helped identify and characterize some specific iMSC subsets. These methods help researchers learn more about the localization and functions of iMSC populations during intestinal morphogenic and homeostatic conditions. Consequently, it is imperative to understand the cellular pathways that regulate their activation and how they interact with surrounding cellular components, particularly during intestinal epithelial regeneration after mucosal injury. This review provides insights into the spatial distribution and functions of identified iMSC subtypes. It focuses on their involvement in intestinal morphogenesis, homeostasis, and regeneration. We reviewed related signaling mechanisms implicated during epithelial and subepithelial stromal cell crosstalk. Future research should focus on elucidating the molecular intermediates of these regulatory pathways to open a new frontier for potential therapeutic targets that can alleviate intestinal mucosa-related injuries. Full article
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Other

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8 pages, 2520 KiB  
Brief Report
Colitis Is Associated with Loss of the Histidine Phosphatase LHPP and Upregulation of Histidine Phosphorylation in Intestinal Epithelial Cells
by Markus Linder, Dritan Liko, Venkatesh Kancherla, Salvatore Piscuoglio and Michael N. Hall
Biomedicines 2023, 11(8), 2158; https://doi.org/10.3390/biomedicines11082158 - 1 Aug 2023
Cited by 6 | Viewed by 1567
Abstract
Protein histidine phosphorylation (pHis) is a posttranslational modification involved in cell cycle regulation, ion channel activity and phagocytosis. Using novel monoclonal antibodies to detect pHis, we previously reported that the loss of the histidine phosphatase LHPP (phospholysine phosphohistidine inorganic pyrophosphate phosphatase) results in [...] Read more.
Protein histidine phosphorylation (pHis) is a posttranslational modification involved in cell cycle regulation, ion channel activity and phagocytosis. Using novel monoclonal antibodies to detect pHis, we previously reported that the loss of the histidine phosphatase LHPP (phospholysine phosphohistidine inorganic pyrophosphate phosphatase) results in elevated pHis levels in hepatocellular carcinoma. Here, we show that intestinal inflammation correlates with the loss of LHPP in dextran sulfate sodium (DSS)-treated mice and in inflammatory bowel disease (IBD) patients. Increased histidine phosphorylation was observed in intestinal epithelial cells (IECs), as determined by pHis immunofluorescence staining of colon samples from a colitis mouse model. However, the ablation of Lhpp did not cause increased pHis or promote intestinal inflammation under physiological conditions or after DSS treatment. Our observations suggest that increased histidine phosphorylation plays a role in colitis, but the loss of LHPP is not sufficient to increase pHis or to cause inflammation in the intestine. Full article
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