scholarly journals CCR6–CCL20-Mediated Immunologic Pathways in Inflammatory Bowel Disease

2018 ◽  
Vol 1 (1) ◽  
pp. 15-29 ◽  
Author(s):  
Ranmali Ranasinghe ◽  
Rajaraman Eri
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Systematic Investigation ◽  
Protective Mechanism ◽  
Food Antigens ◽  
Gut Mucosa ◽  
T Helper Lymphocyte ◽  
Inflammatory Bowel ◽  
Underlying Mechanisms

Inflammatory bowel disease (IBD) has evoked significant interest in human immunobiology given its tactical immune evasion methodologies resulting in acute immune destabilization. IBD comprising Crohn’s disease and Ulcerative colitis manifests as chronic inflammation in the gut mucosa, leading to complexities involving immune dysregulation in the T helper lymphocyte arm, effecting disease pathogenicity. The mucosa of the alimentary canal is constantly exposed to a myriad of food antigens and luminal microorganisms for which a consistent host-protective mechanism is operative in healthy people. Lowered mucosal immune expression which allows penetration of the epithelial barrier by infective pathogenic microbes elicits both innate and adaptive immune responses in the gut, culminating in aberrant intestinal inflammation. Interestingly, the IBD leukocyte repertoire is significantly entwined with chemokine-assisted chemotactic navigation into the sites of inflammation, which is also thought to generate favorable immune-suppressive responses. The functions of the cognate chemokine receptor, CCR6, which binds with its unique ligand CCL20, are expected to tilt the balance between upregulation of homeostatic tolerance and inflammatory pathophysiology. This review aims to critically examine the CCR6-driven immune pathways: TH1/TH2, TH1/TH17, TH17/Treg, IL-23/IL-17, Akt/ERK-1/2, ILC3, and TH9/TH2 for systematic investigation of its underlying mechanisms in the future and to underpin its importance in resolving IBD pathology. Thus, CCR6 occupies an exclusive position in gut immunology which renders it an invaluable therapeutic tool for the production of novel medicaments to treat IBD.

scholarly journals CCR6-CCL20 Signalling Networks in Inflammatory Bowel Disease

2018 ◽  
Author(s):  
Ranmali Ranasinghe ◽  
Rajaraman Eri
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Systematic Investigation ◽  
Protective Mechanism ◽  
Food Antigens ◽  
Gut Mucosa ◽  
T Helper Lymphocyte ◽  
Inflammatory Bowel ◽  
Underlying Mechanisms

Inflammatory bowel disease (IBD) has evoked a significant interest in human immunobiology given its tactical immune evasion methodologies resulting in acute immune destabilization. IBD comprising of Crohn’s disease and Ulcerative colitis manifest as chronic inflammation in the gut mucosa, leading to complexities involving immune dysregulation in the T helper lymphocyte arm effecting disease pathogenicity. The mucosa of the alimentary canal is constantly exposed to a myriad of food antigens and luminal microorganisms for which a consistent host-protective mechanism is operative in healthy people. Lowered mucosal immune expression which allows penetration of the epithelial barrier by infective pathogenic microbes, elicits both innate and adaptive immune responses in the gut culminating in aberrant intestinal inflammation. Interestingly, IBD leukocyte repertoire is significantly entwined with chemokine assisted chemotactic navigation into the sites of inflammation which is also thought to generate favourable immune suppressive responses. The functions of the cognate chemokine receptor, CCR6, which binds with its unique ligand CCL20, are expected to tilt the balance between upregulation of homeostatic tolerance and inflammatory pathophysiology. This review aims at critically examining the CCR6 driven immune pathways; TH1/TH2, TH1/TH17, TH17/ Treg, IL-23/IL-17, Akt/ERK-1 /2, ILC3 for systematic investigation of its underlying mechanisms in the future and to underpin its importance in resolving IBD aetiopathology. Thus, CCR6 occupies an exclusive position in gut immunology which renders it an invaluable therapeutic tool for the production of novel medicaments to treat IBD.

scholarly journals Intestinal Regulatory T Cells as Specialized Tissue-Restricted Immune Cells in Intestinal Immune Homeostasis and Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Justin Jacobse ◽  
Jing Li ◽  
Edmond H. H. M. Rings ◽  
Janneke N. Samsom ◽  
Jeremy A. Goettel
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
Regulatory T Cells ◽  
Treg Cell ◽  
Bowel Disease ◽  
Cell Biology ◽  
Intestinal Inflammation ◽  
Treg Cells ◽  
Food Antigens ◽  
Inflammatory Bowel

FOXP3+ regulatory T cells (Treg cells) are a specialized population of CD4+ T cells that restrict immune activation and are essential to prevent systemic autoimmunity. In the intestine, the major function of Treg cells is to regulate inflammation as shown by a wide array of mechanistic studies in mice. While Treg cells originating from the thymus can home to the intestine, the majority of Treg cells residing in the intestine are induced from FOXP3neg conventional CD4+ T cells to elicit tolerogenic responses to microbiota and food antigens. This process largely takes place in the gut draining lymph nodes via interaction with antigen-presenting cells that convert circulating naïve T cells into Treg cells. Notably, dysregulation of Treg cells leads to a number of chronic inflammatory disorders, including inflammatory bowel disease. Thus, understanding intestinal Treg cell biology in settings of inflammation and homeostasis has the potential to improve therapeutic options for patients with inflammatory bowel disease. Here, the induction, maintenance, trafficking, and function of intestinal Treg cells is reviewed in the context of intestinal inflammation and inflammatory bowel disease. In this review we propose intestinal Treg cells do not compose fixed Treg cell subsets, but rather (like T helper cells), are plastic and can adopt different programs depending on microenvironmental cues.

scholarly journals An Update of Research Animal Models of Inflammatory Bowel Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Zineb Baydi ◽  
Youness Limami ◽  
Loubna Khalki ◽  
Nabil Zaid ◽  
Abdallah Naya ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Animal Models ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Therapeutic Strategies ◽  
Murine Models ◽  
Immune System Dysfunction ◽  
Inflammatory Bowel ◽  
Underlying Mechanisms ◽  
And Shifts

Inflammatory bowel disease (IBD) is a group of chronic disorders that includes two main disease forms, Crohn’s disease, and ulcerative colitis. The understanding of the intestinal inflammation occurring in IBD has been immeasurably advanced by the development of the now numerous murine models of intestinal inflammation. The usefulness of this research tool in IBD arises from a convergence of underlying genetic susceptibility, immune system dysfunction, environmental factors, and shifts in gut microbiota. Due to the multifactorial feature of these diseases, different animal models have been used to investigate the underlying mechanisms and develop potential therapeutic strategies. The results of preclinical efficacy studies often inform the progression of therapeutic strategies. This review describes the distinct feature and limitations of each murine IBD model and discusses the previous and current lessons from the IBD models.

scholarly journals The food additive EDTA aggravates colitis and colon carcinogenesis in mouse models

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rayko Evstatiev ◽  
Adam Cervenka ◽  
Tina Austerlitz ◽  
Gunther Deim ◽  
Maximilian Baumgartner ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Mouse Models ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Food Additives ◽  
Colorectal Carcinogenesis ◽  
Testing Procedures ◽  
Inflammatory Models ◽  
Inflammatory Bowel

AbstractInflammatory bowel disease is a group of conditions with rising incidence caused by genetic and environmental factors including diet. The chelator ethylenediaminetetraacetate (EDTA) is widely used by the food and pharmaceutical industry among numerous other applications, leading to a considerable environmental exposure. Numerous safety studies in healthy animals have revealed no relevant toxicity by EDTA. Here we show that, in the presence of intestinal inflammation, EDTA is surprisingly capable of massively exacerbating inflammation and even inducing colorectal carcinogenesis at doses that are presumed to be safe. This toxicity is evident in two biologically different mouse models of inflammatory bowel disease, the AOM/DSS and the IL10−/− model. The mechanism of this effect may be attributed to disruption of intercellular contacts as demonstrated by in vivo confocal endomicroscopy, electron microscopy and cell culture studies. Our findings add EDTA to the list of food additives that might be detrimental in the presence of intestinal inflammation, but the toxicity of which may have been missed by regulatory safety testing procedures that utilize only healthy models. We conclude that the current use of EDTA especially in food and pharmaceuticals should be reconsidered. Moreover, we suggest that intestinal inflammatory models should be implemented in the testing of food additives to account for the exposure of this primary organ to environmental and dietary stress.

scholarly journals Pathomechanisms of Oxidative Stress in Inflammatory Bowel Disease and Potential Antioxidant Therapies

2017 ◽  
Vol 2017 ◽  
pp. 1-18 ◽  
Author(s):  
Tian Tian ◽  
Ziling Wang ◽  
Jinhua Zhang
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Defense Mechanisms ◽  
Gastrointestinal Disease ◽  
Mucosal Immune Response ◽  
Stress Signaling ◽  
Substantial Progress ◽  
Inflammatory Bowel ◽  
Underlying Mechanisms

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease whose incidence has risen worldwide in recent years. Accumulating evidence shows that oxidative stress plays an essential role in the pathogenesis and progression of IBD. This review highlights the generation of reactive oxygen species (ROS) and antioxidant defense mechanisms in the gastrointestinal (GI) tract, the involvement of oxidative stress signaling in the initiation and progression of IBD and its relationships with genetic susceptibility and the mucosal immune response. In addition, potential therapeutic strategies for IBD that target oxidative stress signaling are reviewed and discussed. Though substantial progress has been made in understanding the role of oxidative stress in IBD in humans and experimental animals, the underlying mechanisms are still not well defined. Thus, further studies are needed to validate how oxidative stress signaling is involved in and contributes to the development of IBD.

Sign in / Sign up

Export Citation Format

Share Document