Cellular and Molecular Gastroenterology and Hepatology

BACKGROUND & AIMS: The presence of myenteric plexitis in the proximal resection margins is a predictive factor of early postoperative recurrence in Crohn's disease. To decipher the mechanisms leading to their formation, T cell interactions with enteric neural cells were studied in vitro and in vivo. METHODS: T cells close to myenteric neural cells were retrospectively quantified in ileocolonic resections from 9 control subjects with cancer and 20 patients with Crohn's disease...

BACKGROUND AND AIMS: As the most abundant memory T cells and major source of tumor necrosis factor α (TNF-α) in the intestinal mucosa of Crohn's disease (CD) patients, CD4+ tissue-resident memory T (TRM ) cells play a critical role in CD pathogenesis. We investigated the role of metabolic reprogramming in the regulation of proinflammatory and apoptosis-resistant phenotype for CD4+ TRM cells. METHODS: CD4+ TRM cells were collected from intestinal resection tissues from control and CD patients...

BACKGROUND & AIMS: Excessive alcohol consumption can lead to alcohol-associated liver disease, a spectrum of conditions ranging from steatosis to fibrosis and cirrhosis. Bile acids regulate metabolic pathways by binding to cellular and nuclear receptors, and they also interact with the gut microbiome to control microbial overgrowth. Fibroblast growth factor 19 (FGF-19) is an ileum-derived hormone induced and released in response to bile acid activation of the nuclear receptor farnesoid X receptor...

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Stromal cell populations have a central role in providing signals that support the maintenance, differentiation and function of the intestinal epithelium. The behaviour and fate of epithelial cells is directed by the spatial organisation of stromal cells that either sustain stem and progenitor cell identity or drive differentiation. A combination of single-cell analyses, mouse models and organoid co-culture assays have provided insight into the diversity of signals delivered by stromal cells. Signalling gradients are established and fine-tuned by the expression of both signalling agonists and antagonists along the crypt-villus axis...

Telocytes are unique mesenchymal cells characterized by multiple remarkably long cytoplasmic extensions that extend hundreds of micron away from the cell body. Through these extensions, telocytes establish a three-dimensional network by connecting with other telocytes and various cell types within the tissue. In the intestine, telocytes have emerged as an essential component of the stem cell niche, providing Wnt proteins that are critical for the proliferation of stem and progenitor cells. However, the analysis of single cell RNA sequencing has revealed other stromal populations and mechanisms for niche organization, raising questions about the role of telocytes as a component of the stem cell niche...

Numerous recent studies using single cell RNA sequencing (scRNA-seq) and spatial transcriptomics have shown the vast cell heterogeneity, including epithelial, immune and stromal cells, present in the normal human stomach and at different stages of gastric carcinogenesis. Fibroblasts within the metaplastic and dysplastic mucosal stroma represent key contributors to the carcinogenic microenvironment in the stomach. The heterogeneity of fibroblast populations is present in the normal stomach, but plasticity within these populations underlies their alterations in association with both metaplasia and dysplasia...

BACKGROUND & AIMS: Hepatic ischemia-reperfusion injury (HIRI) often occurs in liver surgery such as partial hepatectomy and liver transplantation, in which myeloid macrophage-mediated inflammation plays a critical role. Cell division cycle 42 (Cdc42) regulates cell migration, cytoskeleton rearrangement and cell polarity. In this study, we aim to explore the role of myeloid Cdc42 in HIRI. METHODS: Mouse HIRI models were established with 1 hr ischemia followed by 12 hr reperfusion in myeloid Cdc42 knockout (Cdc42mye ) and Cdc42flox mice...

BACKGROUND & AIMS: Epithelial disruption in eosinophilic esophagitis (EoE) encompasses both impaired differentiation and diminished barrier integrity. We have shown that lysyl oxidase (LOX), a collagen cross-linking enzyme, is upregulated in the esophageal epithelium in EoE. However, the functional roles of LOX in the esophageal epithelium remains unknown. METHODS: We investigated roles for LOX in the human esophageal epithelium using 3-dimensional organoid and air-liquid interface cultures stimulated with interleukin (IL)-13 to recapitulate the EoE inflammatory milieu, followed by single-cell RNA sequencing, quantitative reverse transcription-polymerase chain reaction, western blot, histology, and functional analyses of barrier integrity...

BACKGROUND: In the classical form of α1-antitrypsin deficiency (ATD), the misfolded α1-antitrypsin Z (ATZ) variant accumulates in the endoplasmic reticulum (ER) of liver cells. A gain-of-function proteotoxic mechanism is responsible for chronic liver disease in a sub-group of homozygotes. Proteostatic response pathways, including conventional ERAD and autophagy, have been proposed as the mechanisms that allow cellular adaptation and presumably protection from the liver disease phenotype...

The complex, bidirectional interactions between the brain, the gut and the gut microbes are best referred to as the Brain Gut Microbiome system. Animal and clinical studies have identified specific signaling mechanisms within this system, with gut microbes communicating to the brain through neuronal, endocrine, and immune pathways. The brain, in turn, modulates the composition and function of the gut microbiota through the autonomic nervous system, regulating gut motility, secretion and permeability, and the release of hormones impacting microbial gene expression...

BACKGROUND & AIMS: This review was developed to provide a thorough and effective update on models relevant to esophageal metaplasia, dysplasia, and carcinogenesis, focusing on the advantages and limitations of different models of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). METHODS: This expert review was written on the basis of a thorough review of the literature combined with expert interpretation of the state of the field. We emphasized advances over the years 2012-2023 and provided detailed information related to the characterization of established human esophageal cell lines...

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Bearing a dismal 5-year survival rate, pancreatic ductal adenocarcinoma (PDAC) is a challenging disease that features a unique fibroinflammatory tumor microenvironment (TME). As major components of the PDAC TME, cancer associated fibroblasts (CAFs) are still poorly understood and their contribution to the several hallmarks of PDAC, such as resistance to therapies, immunosuppression, and high incidence of metastasis, is likely underestimated. There have been encouraging advances in our understanding of these fascinating cells, but many controversies remain, leaving the field still actively exploring the full scope of their contributions in PDAC progression...

Eosinophilic esophagitis (EoE) is an emerging form of food allergy that exerts a significant clinical and financial burden worldwide. EoE is clinically characterized by eosinophil-rich inflammatory infiltrates in esophageal mucosa and esophageal dysfunction. Remodeling events in esophageal epithelium and lamina propria also frequently occur in patients with EoE. Because subepithelial fibrosis is associated with esophageal stricture, the most severe consequence of EoE, there exists an urgent need for a deeper understanding of the molecular mechanisms mediating fibrosis in EoE...