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

A significant overlap exists between spondyloarthritis (SpA) and inflammatory bowel disease (IBD), particularly in the IL-23/IL-17 pathway. Shared immunologic mechanisms include aberrant innate immune responses, an excess of Th1/Th17-mediated immunity, and inadequate immune regulation. Many genetic factors associated with IBD are involved in host–pathogen interactions and intestinal barrier function, and the intestinal microbiota do appear to play an important role in disease development. Hence the current hypothesis for IBD pathogenesis is that it stems from a dysregulated immune response to intestinal microbiota in a genetically susceptible host. In SpA, evidence for a role of intestinal microbiota is less abundant, but given the overlap with IBD, it is plausible that gut microbiota are important players in SpA pathogenesis as well. However, there are significant genetic differences between these two conditions, as well as differing responses to biologic therapy.

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The role and pathophysiological relevance of membrane transporter PepT1 in intestinal inflammation and inflammatory bowel disease

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00477.2011 ◽

2012 ◽

Vol 302 (5) ◽

pp. G484-G492 ◽

Cited By ~ 64

Author(s):

Sarah A. Ingersoll ◽

Saravanan Ayyadurai ◽

Moiz A. Charania ◽

Hamed Laroui ◽

Yutao Yan ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Intestinal Inflammation ◽

Innate Immune ◽

Peptide Transport ◽

Innate Immune Responses ◽

Colon Cells ◽

Proinflammatory Responses ◽

Inflammatory Bowel ◽

Chronic Intestinal Inflammation

Intestinal inflammation is characterized by epithelial disruption, leading to loss of barrier function and the recruitment of immune cells, including neutrophils. Although the mechanisms are not yet completely understood, interactions between environmental and immunological factors are thought to be critical in the initiation and progression of intestinal inflammation. In recent years, it has become apparent that the di/tripeptide transporter PepT1 may play an important role in the pathogenesis of such inflammation. In healthy individuals, PepT1 is primarily expressed in the small intestine and transports di/tripeptides for metabolic purposes. However, during chronic inflammation such as that associated with inflammatory bowel disease, PepT1 expression is upregulated in the colon, wherein the protein is normally expressed either minimally or not at all. Several recent studies have shown that PepT1 binds to and transports various bacterial di/tripeptides into colon cells, leading to activation of downstream proinflammatory responses via peptide interactions with innate immune receptors. In the present review, we examine the relationship between colonic PepT1-mediated peptide transport in the colon and activation of innate immune responses during disease. It is important to understand the mechanisms of PepT1 action during chronic intestinal inflammation to develop future therapies addressing inappropriate immune activation in the colon.

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Nonhypoalbuminemic Inflammatory Bowel Disease in Dogs as Disease Model

Inflammatory Bowel Diseases ◽

10.1093/ibd/izab064 ◽

2021 ◽

Author(s):

Juan Hernandez ◽

Elodie Rouillé ◽

Florian Chocteau ◽

Marie Allard ◽

Karine Haurogné ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Immune Responses ◽

Bowel Disease ◽

Interindividual Variability ◽

Expression Patterns ◽

Disease Model ◽

Protein Loss ◽

Tissue Concentrations ◽

Inflammatory Bowel ◽

Antibody Levels

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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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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