Related Experiment Video
Updated: May 29, 2026
03:23
Three-Dimensional Cell Culture Models to Investigate the Epithelial Barrier in Eosinophilic Esophagitis
Published on: May 10, 2024
CCR3 Blockade Attenuates Eosinophilic Ileitis and Associated Remodeling
Joanne C Masterson1, Eóin N McNamee, Paul Jedlicka
1Section of Pediatric Gastroenterology, Hepatology and Nutrition-Digestive Health Institute, Children's Hospital Colorado, Aurora, Colorado, USA.
The American Journal of Pathology
|September 28, 2011
Summary
Eosinophils drive intestinal remodeling and stricture formation in inflammatory bowel disease (IBD). Reducing eosinophils significantly decreased IBD-associated tissue damage, highlighting eosinophils as a potential therapeutic target for IBD.
Area of Science:
- Gastroenterology
- Immunology
- Pathology
Background:
- Intestinal remodeling and stricture formation are common complications of inflammatory bowel disease (IBD).
- The role of eosinophils, which are increased in IBD tissues, in IBD-associated intestinal remodeling remains unclear.
Purpose of the Study:
- To investigate the role of eosinophils in intestinal remodeling and stricture formation in a murine model of chronic eosinophilic ileitis.
Main Methods:
- Utilized a spontaneous eosinophilic Crohn's-like mouse model (SAMP1/SkuSlc).
- Assessed histological and molecular features of ileitis and remodeling over 40 weeks using immunohistochemistry, histomorphometry, flow cytometry, and real-time RT-PCR.
- Quantified collagen protein using Sircol assay.
- Administered CCR3-specific antibody to reduce eosinophils.
Main Results:
- Ileitis and remodeling progressed over 40 weeks, correlating with increased mucosal and submucosal eosinophilia and fibronectin expression.
- CCR3-specific antibody treatment significantly reduced goblet cell hyperplasia, muscularis propria hypertrophy, villus blunting, and inflammatory/remodeling gene expression.
- Eosinophil reduction also decreased mesenteric lymph node cellularity, including T- and B-lymphocytes.
Conclusions:
- Eosinophils play a significant role in driving intestinal remodeling and inflammation in IBD.
- Targeting eosinophils represents a potential novel therapeutic strategy for managing IBD-associated intestinal remodeling and stricture formation.
Related Concept Videos
01:25Inflammatory Bowel Disease III: Crohn's Disease
Crohn’s disease is a chronic, relapsing form of inflammatory bowel disease characterized by segmental, transmural inflammation that can affect any part of the gastrointestinal tract. Its pathogenesis arises from a combination of genetic susceptibility, environmental exposures, epithelial barrier dysfunction, and immune dysregulation. Together, these factors lead to an exaggerated immune response against components of the gut microbiome.Genetic and Environmental InfluencesMultiple genetic...
01:20Inflammatory Bowel Disease II: Ulcerative Colitis
Ulcerative colitis is a chronic inflammatory disorder of the colon characterized by continuous mucosal inflammation that typically begins in the rectum and extends proximally in a uniform pattern. Its pathogenesis involves a complex interplay of genetic predisposition, immune dysregulation, and environmental influences. These factors converge to impair the colon’s epithelial defenses and promote an exaggerated inflammatory response against luminal contents.Breakdown of the Mucosal BarrierA...
01:30Inflammatory Bowel Disease II: Crohn's Disease
Introduction
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by transmural...
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by transmural...
01:22Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
01:17Chronic Bowel Disorders: Introduction
Chronic bowel diseases are a group of long-term conditions affecting the digestive tract, characterized by inflammation and damage to the gut lining. These conditions primarily include irritable bowel syndrome and inflammatory bowel disease.
Irritable Bowel Syndrome (IBS) is a common disorder affecting the gastrointestinal tract. The distinctive feature is recurrent abdominal pain associated with altered bowel movements, manifesting as constipation, diarrhea, or fluctuating between both. The...
Irritable Bowel Syndrome (IBS) is a common disorder affecting the gastrointestinal tract. The distinctive feature is recurrent abdominal pain associated with altered bowel movements, manifesting as constipation, diarrhea, or fluctuating between both. The...
01:24Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab (Humira),...