TRIM21 Negatively Regulates Intestinal Mucosal Inflammation through Inhibition of Th1/Th17 Cell Immune Responses in Inflammatory Bowel Disease

Abstract Background The incidence of inflammatory bowel disease (IBD) is increasing worldwide, emphasizing the need of relevant models, as dogs spontaneously affected by IBD may be, for better knowledge of the disease’s physiopathology. Methods We studied 22 client-owned dogs suffering from IBD without protein loss and 14 control dogs. Biopsies were obtained from the duodenum, ileum, and colon. Inflammatory grade was assessed by histopathology, immunohistochemistry, and chemokine analysis. The expression of Toll-like receptors (TLR) in mucosa was immunohistochemically evaluated. Antibody levels against bacterial ligands (lipopolysaccharide [LPS] and flagellin) were measured in sera using enzyme-linked immunoassay. Results Dogs with IBD showed low to severe clinical disease. Histopathologically, the gut of dogs with IBD did not exhibit significant alterations compared with controls except in the colon. The number of CD3+ T lymphocytes was decreased in the ileum and colon of dogs with IBD compared with controls, whereas the numbers of Foxp3+, CD20+, and CD204+ cells were similar in the 2 groups. Three chemokines, but no cytokines, were detected at the protein level in the mucosa, and the disease poorly affected their tissue concentrations. Dogs with IBD exhibited higher serum reactivity against LPS and flagellin than controls but similar immunoreactivity against the receptors TLR4 and TLR5. In addition, TLR2 and TLR9 showed similar expression patterns in both groups of dogs. Conclusions Our data described dysregulated immune responses in dogs affected by IBD without protein loss. Despite fairly homogeneous dog cohorts, we were still faced with interindividual variability, and new studies with larger cohorts are needed to validate the dog as a model.

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Tu1818 - Vitamin a Modulates Mucosal Inflammation by Augmenting Th1/Th17 Differentiation in Inflammatory Bowel Disease

Gastroenterology ◽

10.1016/s0016-5085(18)33444-9 ◽

2018 ◽

Vol 154 (6) ◽

pp. S-1028

Author(s):

Ritika Rampal ◽

Mohamad Nahidul Wari ◽

Amit K. Singh ◽

Ujjwal K. Das ◽

Sawan Bopanna ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Vitamin A ◽

Bowel Disease ◽

Mucosal Inflammation ◽

Inflammatory Bowel ◽

Th17 Differentiation

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A Comprehensive Review and Update on the Pathogenesis of Inflammatory Bowel Disease

Journal of Immunology Research ◽

10.1155/2019/7247238 ◽

2019 ◽

Vol 2019 ◽

pp. 1-16 ◽

Cited By ~ 35

Author(s):

Qingdong Guan

Keyword(s):

Inflammatory Bowel Disease ◽

Immune Responses ◽

Bowel Disease ◽

Genetic Factors ◽

Intestinal Inflammation ◽

Adaptive Immune Responses ◽

Adaptive Immune ◽

Host Genetic ◽

Inflammatory Bowel ◽

Host Genetic Factors

Inflammatory bowel disease (IBD) is a chronic and life-threating inflammatory disease of gastroenteric tissue characterized by episodes of intestinal inflammation. The pathogenesis of IBD is complex. Recent studies have greatly improved our knowledge of the pathophysiology of IBD, leading to great advances in the treatment as well as diagnosis of IBD. In this review, we have systemically reviewed the pathogenesis of IBD and highlighted recent advances in host genetic factors, gut microbiota, and environmental factors and, especially, in abnormal innate and adaptive immune responses and their interactions, which may hold the keys to identify novel predictive or prognostic biomarkers and develop new therapies.

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Histamine Receptor 2 is Required to Suppress Innate Immune Responses to Bacterial Ligands in Patients with Inflammatory Bowel Disease

Inflammatory Bowel Diseases ◽

10.1097/mib.0000000000000825 ◽

2016 ◽

Vol 22 (7) ◽

pp. 1575-1586 ◽

Cited By ~ 21

Author(s):

Sylwia Smolinska ◽

David Groeger ◽

Noelia Rodriguez Perez ◽

Elisa Schiavi ◽

Ruth Ferstl ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Immune Responses ◽

Bowel Disease ◽

Histamine Receptor ◽

Innate Immune ◽

Innate Immune Responses ◽

Inflammatory Bowel

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Factors affecting clinical decision-making in inflammatory bowel disease and the role of point-of-care calprotectin

Therapeutic Advances in Gastroenterology ◽

10.1177/1756283x17744739 ◽

2018 ◽

Vol 11 ◽

pp. 1756283X1774473 ◽

Cited By ~ 9

Author(s):

Yannick Derwa ◽

Christopher J.M. Williams ◽

Ruchit Sood ◽

Saqib Mumtaz ◽

M. Hassan Bholah ◽

...

Keyword(s):

Decision Making ◽

Inflammatory Bowel Disease ◽

Disease Activity ◽

Medical Therapy ◽

Bowel Disease ◽

Clinical Decision Making ◽

Point Of Care ◽

Clinical Decision ◽

Mucosal Inflammation ◽

Inflammatory Bowel

Objectives: Patient-reported symptoms correlate poorly with mucosal inflammation. Clinical decision-making may, therefore, not be based on objective evidence of disease activity. We conducted a study to determine factors associated with clinical decision-making in a secondary care inflammatory bowel disease (IBD) population, using a cross-sectional design. Methods: Decisions to request investigations or escalate medical therapy were recorded from outpatient clinic encounters in a cohort of 276 patients with ulcerative colitis (UC) or Crohn’s disease (CD). Disease activity was assessed using clinical indices, self-reported flare and faecal calprotectin ≥ 250 µg/g. Demographic, disease-related and psychological factors were assessed using validated questionnaires. Logistic regression was performed to determine the association between clinical decision-making and symptoms, mucosal inflammation and psychological comorbidity. Results: Self-reported flare was associated with requesting investigations in CD [odds ratio (OR) 5.57; 95% confidence interval (CI) 1.84–17.0] and UC (OR 10.8; 95% CI 1.8–64.3), but mucosal inflammation was not (OR 1.62; 95% CI 0.49–5.39; and OR 0.21; 95% CI 0.21–1.05, respectively). Self-reported flare (OR 7.96; 95% CI 1.84–34.4), but not mucosal inflammation (OR 1.67; 95% CI 0.46–6.13) in CD, and clinical disease activity (OR 10.36; 95% CI 2.47–43.5) and mucosal inflammation (OR 4.26; 95% CI 1.28–14.2) in UC were associated with escalation of medical therapy. Almost 60% of patients referred for investigation had no evidence of mucosal inflammation. Conclusions: Apart from escalation of medical therapy in UC, clinical decision-making was not associated with mucosal inflammation in IBD. The use of point-of-care calprotectin testing may aid clinical decision-making, improve resource allocation and reduce costs in IBD.

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Inflammatory bowel disease

10.1093/med/9780199568741.003.0203 ◽

2018 ◽

Author(s):

Satish Keshav ◽

Alexandra Kent

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Age Of Onset ◽

Anal Verge ◽

Age At Onset ◽

Mucosal Inflammation ◽

Gi Tract ◽

Disease Extent ◽

Inflammatory Bowel ◽

Different Characteristics

Inflammatory bowel disease (IBD) encompasses ulcerative colitis (UC) and Crohn’s disease (CD). Both conditions cause chronic relapsing inflammation in the gastrointestinal (GI) tract, but have different characteristics. UC causes diffuse mucosal inflammation limited to the colon, extending proximally from the anal verge, with the rectum involved in 95% of patients. UC is described in terms of the disease extent: proctitis (confined to the rectum), proctosigmoiditis (disease confined to the recto-sigmoid colon), distal disease (distal to the splenic flexure), and pan-colitis (the entire large intestine). The extent of disease can change, with proximal extension seen in approximately a third of patients with proctitis, although there is great variation between studies. CD causes inflammation that can affect the entire thickness of the wall of the intestine, and is not confined to the mucosa. CD can affect any part of the GI tract. The terminal ileum is affected in approximately 80% of cases, the colon in approximately 60% of cases, and the rectum and perianal region in approximately 40% of cases. CD is classified by location (ileal, colonic, ileocolonic, upper GI tract), by the presence of stricturing or penetrating disease, and by the age of onset (before or after the age of 40). Penetrating disease refers to the development of fistulae, which can lead to complications such as abscesses or perforations. An earlier age at onset is associated with more complicated disease. The diagnosis of UC or CD is established through a combination of clinical, endoscopic, radiological, and histological criteria rather than by any single modality. Occasionally, it is not possible to establish an unequivocal diagnosis of CD or UC in IBD, and a third category, accounting for nearly 10% of cases, is used, termed IBD unclassified.

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Colorectal Cancer in Inflammatory Bowel Disease

Clinics in Colon and Rectal Surgery ◽

10.1055/s-0040-1713748 ◽

2020 ◽

Vol 33 (05) ◽

pp. 305-317

Author(s):

Martina Nebbia ◽

Nuha A. Yassin ◽

Antonino Spinelli

Keyword(s):

Colorectal Cancer ◽

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Severe Disease ◽

Critical Role ◽

Mucosal Inflammation ◽

Surgical Approaches ◽

Increased Risk ◽

Significant Difference ◽

Inflammatory Bowel

AbstractPatients with inflammatory bowel disease (IBD) are at an increased risk for developing colorectal cancer (CRC). However, the incidence has declined over the past 30 years, which is probably attributed to raise awareness, successful CRC surveillance programs and improved control of mucosal inflammation through chemoprevention. The risk factors for IBD-related CRC include more severe disease (as reflected by the extent of disease and the duration of poorly controlled disease), family history of CRC, pseudo polyps, primary sclerosing cholangitis, and male sex. The molecular pathogenesis of inflammatory epithelium might play a critical role in the development of CRC. IBD-related CRC is characterized by fewer rectal tumors, more synchronous and poorly differentiated tumors compared with sporadic cancers. There is no significant difference in sex distribution, stage at presentation, or survival. Surveillance is vital for the detection and subsequently management of dysplasia. Most guidelines recommend initiation of surveillance colonoscopy at 8 to 10 years after IBD diagnosis, followed by subsequent surveillance of 1 to 2 yearly intervals. Traditionally, surveillance colonoscopies with random colonic biopsies were used. However, recent data suggest that high definition and chromoendoscopy are better methods of surveillance by improving sensitivity to previously “invisible” flat dysplastic lesions. Management of dysplasia, timing of surveillance, chemoprevention, and the surgical approaches are all areas that stimulate various discussions. The aim of this review is to provide an up-to-date focus on CRC in IBD, from laboratory to bedside.

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