scholarly journals The Regulation of Intestinal Inflammation and Cancer Development by Type 2 Immune Responses

2020 ◽  
Vol 21 (24) ◽  
pp. 9772
Author(s):  
Reyes Gamez-Belmonte ◽  
Lena Erkert ◽  
Stefan Wirtz ◽  
Christoph Becker
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Immune Responses ◽  
Immune Cells ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Clinical Care ◽  
Important Barrier ◽  
Inflammatory Bowel

The gut is among the most complex organs of the human body. It has to exert several functions including food and water absorption while setting up an efficient barrier to the outside world. Dysfunction of the gut can be life-threatening. Diseases of the gastrointestinal tract such as inflammatory bowel disease, infections, or colorectal cancer, therefore, pose substantial challenges to clinical care. The intestinal epithelium plays an important role in intestinal disease development. It not only establishes an important barrier against the gut lumen but also constantly signals information about the gut lumen and its composition to immune cells in the bowel wall. Such signaling across the epithelial barrier also occurs in the other direction. Intestinal epithelial cells respond to cytokines and other mediators of immune cells in the lamina propria and shape the microbial community within the gut by producing various antimicrobial peptides. Thus, the epithelium can be considered as an interpreter between the microbiota and the mucosal immune system, safeguarding and moderating communication to the benefit of the host. Type 2 immune responses play important roles in immune-epithelial communication. They contribute to gut tissue homeostasis and protect the host against infections with helminths. However, they are also involved in pathogenic pathways in inflammatory bowel disease and colorectal cancer. The current review provides an overview of current concepts regarding type 2 immune responses in intestinal physiology and pathophysiology.

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

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
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.

Bringing to Light the Risk of Colorectal Cancer in Inflammatory Bowel Disease: Mucosal Glycosylation as a Key Player

2021 ◽  
Author(s):  
Eduarda Leite-Gomes ◽  
Ana M Dias ◽  
Catarina M Azevedo ◽  
Beatriz Santos-Pereira ◽  
Mariana Magalhães ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Molecular Mechanisms ◽  
Intestinal Inflammation ◽  
Serum Proteins ◽  
Major Complication ◽  
Cancer Pathogenesis ◽  
Colon Inflammation ◽  
Inflammatory Bowel

Abstract Colitis-associated cancer is a major complication of inflammatory bowel disease remaining an important clinical challenge in terms of diagnosis, screening, and prognosis. Inflammation is a driving factor both in inflammatory bowel disease and cancer, but the mechanism underlying the transition from colon inflammation to cancer remains to be defined. Dysregulation of mucosal glycosylation has been described as a key regulatory mechanism associated both with colon inflammation and colorectal cancer development. In this review, we discuss the major molecular mechanisms of colitis-associated cancer pathogenesis, highlighting the role of glycans expressed at gut epithelial cells, at lamina propria T cells, and in serum proteins in the regulation of intestinal inflammation and its progression to colon cancer, further discussing its potential clinical and therapeutic applications.

scholarly journals Colorectal Cancer in Inflammatory Bowel Disease

2018 ◽  
Vol 31 (03) ◽  
pp. 168-178 ◽  
Author(s):  
Peter Higgins ◽  
Ryan Stidham
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Detection Techniques ◽  
Clinical Scenarios ◽  
Increased Risk ◽  
Consensus Statements ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

AbstractPatients with inflammatory bowel disease (IBD) are at significantly increased risk of colorectal cancer (CRC), principally resulting from the pro-neoplastic effects of chronic intestinal inflammation. Epidemiologic studies continue to highlight the increased risk of CRC in IBD. However, the incidence has declined over the past 30 years, attributed to both successful CRC-surveillance programs and improved control of mucosal inflammation. Risk factors that further increase the risk of IBD-related CRC include disease duration, extent and severity, the presence of inflammatory pseudopolyps, coexistent primary sclerosing cholangitis, and a family history of CRC. All major professional societies agree that IBD-CRC surveillance should occur more frequently than in the general population. Yet, guidelines and consensus statements differ on the surveillance schedule and preferred method of surveillance. Improved sensitivity to previously “invisible” flat dysplastic lesions using high definition and chromoendoscopy methods has resulted in many guidelines abandoning requirements for random untargeted biopsies of the colon. While colonic dysplasia remains a worrisome finding, and several clinical scenarios remain best addressed by total proctocolectomy due to concerns of synchronous undetected lesions and the unpredictable tempo of progression to malignancy, better detection techniques have also increased opportunities for endoscopic resection of dysplastic lesions that can be clearly delineated. Finally, the expanding armamentarium of medical options in IBD, including anti-tumor necrosis factor and anti-adhesion biologic therapies, have substantially improved our ability to control severe inflammation and likely reduce the risk of CRC over time.

scholarly journals Roseburia intestinalis: A Beneficial Gut Organism From the Discoveries in Genus and Species

2021 ◽  
Vol 11 ◽  
Author(s):  
Kai Nie ◽  
Kejia Ma ◽  
Weiwei Luo ◽  
Zhaohua Shen ◽  
Zhenyu Yang ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Energy Homeostasis ◽  
Intestinal Inflammation ◽  
Potential Therapeutic Role ◽  
Health And Disease ◽  
Inflammatory Bowel ◽  
Curved Rod

Roseburia intestinalis is an anaerobic, Gram-positive, slightly curved rod-shaped flagellated bacterium that produces butyrate in the colon. R. intestinalis has been shown to prevent intestinal inflammation and maintain energy homeostasis by producing metabolites. Evidence shows that this bacterium contributes to various diseases, such as inflammatory bowel disease, type 2 diabetes mellitus, antiphospholipid syndrome, and atherosclerosis. This review reveals the potential therapeutic role of R. intestinalis in human diseases. Patients with inflammatory bowel disease exhibit significant changes in R. intestinalis abundance, and they may benefit a lot from modulations targeting R. intestinalis. The data reviewed here demonstrate that R. intestinalis plays its role in regulating barrier homeostasis, immune cells, and cytokine release through its metabolite butyrate, flagellin and other. Recent advancements in the application of primary culture technology, culture omics, single-cell sequencing, and metabonomics technology have improved research on Roseburia and revealed the benefits of this bacterium in human health and disease treatment.

scholarly journals P085 Deep profiling of the circulating immune cell landscape in inflammatory bowel disease by mass cytometry

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S177-S177
Author(s):  
V Horn ◽  
Z Borek ◽  
E Mantzivi ◽  
M Urbicht ◽  
D Boesel ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Immune Cells ◽  
Bowel Disease ◽  
Immune Cell ◽  
Intestinal Inflammation ◽  
Therapy Monitoring ◽  
Mass Cytometry ◽  
Adaptive Immune Cells ◽  
Healthy Donors ◽  
Inflammatory Bowel

Abstract Background A complex interplay of innate and adaptive immune cells maintains intestinal homeostasis. In inflammatory bowel disease (IBD), the fragile balance between regulatory and inflammatory cell subsets breaks down. The latter are recruited to the gut where they sustain intestinal inflammation and lead to tissue destruction. Due to re-circulation and gut-homing processes, the circulating immune cell compartment experiences profound changes that reflect disease activity. Meanwhile, single-cell techniques like mass cytometry have become a powerful technology to shed a light on the heterogeneity and dynamics of immune cells. As obtaining intestinal biopsies from inflamed gut is invasive and poses patients at risk, diagnostics and therapy monitoring from ‘liquid biopsies’ would be a great advance. A deeper understanding of the circulating immune cell landscape in IBD pre- and post-treatment could significantly contribute to IBD patient management by early prediction of therapy response. Methods Whole blood from 24 IBD patients—including 16 ulcerative colitis (UC) and 6 Crohn’s disease (CD) patients before treatment—and 18 age- and sex-matched healthy donors (HDs) was incubated with proteomic stabiliser and frozen. Upon thawing, cell suspensions were Palladium barcoded, stained with a 37-marker panel and acquired on a Helios mass cytometer. The generated dataset was normalised, de-barcoded and subsequently analysed. Results Using dimensionality reduction and neural-network-based algorithms, we faithfully identified different circulating immune subsets in healthy donors and IBD patients. Our preliminary analysis revealed altered myeloid cell populations, like neutrophils and macrophages, in IBD patients. In line with an activation of the innate immune system, we observed a considerable increase in the neutrophil compartment compared with healthy donors. Moreover, patterns of marker expression within different subsets showed substantial differences between healthy donors, CD and UC patients. Conclusion Here, we show a mass cytometry panel that identifies the circulating immune cell landscape and shows major differences between healthy donors, CD and UC patients.

TIPE2 Promotes Tumor Initiation But Inhibits Tumor Progression in Murine Colitis-Associated Colon Cancer

2021 ◽  
Author(s):  
Zienab Etwebi ◽  
Jason R Goldsmith ◽  
Mayassa Bou-Dargham ◽  
Yuhua Tian ◽  
Ryan Hood ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Colon Cancer ◽  
Tumor Progression ◽  
Immune Cells ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Suppressor Cells ◽  
The United States ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

Abstract Background Colorectal cancer (CRC) is the third leading cause of cancer in the United States, and inflammatory bowel disease patients have an increased risk of developing CRC due to chronic intestinal inflammation with it being the cause of death in 10% to 15% of inflammatory bowel disease patients. TIPE2 (TNF-alpha-induced protein 8-like 2) is a phospholipid transporter that is highly expressed in immune cells and is an important regulator of immune cell function. Methods The azoxymethane/dextran sulfate sodium murine model of colitis-associated colon cancer (CAC) was employed in Tipe2 –/– and wild-type mice, along with colonoid studies, to determine the role of TIPE2 in CAC. Results Early on, loss of TIPE2 led to significantly less numbers of visible tumors, which was in line with its previously described role in myeloid-derived suppressor cells. However, as time went on, loss of TIPE2 promoted tumor progression, with larger tumors appearing in Tipe2 –/– mice. This was associated with increased interleukin-22/STAT3 phosphorylation signaling. Similar effects were also observed in primary colonoid cultures, together demonstrating that TIPE2 also directly regulated colonocytes in addition to immune cells. Conclusions This work demonstrates that TIPE2 has dual effects in CAC. In the colonocytes, it works as a tumor suppressor. However, in the immune system, TIPE2 may promote tumorigenesis through suppressor cells or inhibit it through IL-22 secretion. Going forward, this work suggests that targeting TIPE2 for CRC therapy requires cell- and pathway-specific approaches and serves as a cautionary tale for immunotherapy approaches in general in terms of colon cancer, as intestinal inflammation can both promote and inhibit cancer.

scholarly journals Inflammatory bowel disease, colorectal cancer and type 2 diabetes mellitus: The links

BBA Clinical ◽  
2016 ◽  
Vol 5 ◽  
pp. 16-24 ◽  
Author(s):  
Abdo Jurjus ◽  
Assad Eid ◽  
Sahar Al Kattar ◽  
Marie Noel Zeenny ◽  
Alice Gerges-Geagea ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Colorectal Cancer ◽  
Type 2 Diabetes ◽  
Inflammatory Bowel Disease ◽  
Type 2 Diabetes Mellitus ◽  
Bowel Disease ◽  
Inflammatory Bowel

scholarly journals Type 2 immunity in intestinal homeostasis and inflammatory bowel disease

2021 ◽  
Author(s):  
Xinxin Luo ◽  
Eduardo J. Villablanca
Keyword(s):  
Inflammatory Bowel Disease ◽  
Immune Responses ◽  
Bowel Disease ◽  
Tissue Repair ◽  
Lymphoid Cells ◽  
Helminth Parasites ◽  
Cellular Mechanisms ◽  
Intestinal Homeostasis ◽  
Inflammatory Bowel

Type 2 immune responses commonly emerge during allergic reactions or infections with helminth parasites. Most of the cytokines associated with type 2 immune responses are IL-4, IL-5, and IL13, which are mainly produced by T helper 2 cells (TH2), eosinophils, basophils, mast cells, and group 2 innate lymphoid cells (ILC2s). Over the course of evolution, humans have developed type 2 immune responses to fight infections and to protect tissues from the potential collateral damage caused by inflammation. For example, worm parasites induce potent type 2 immune responses, which are needed to simultaneously clear the pathogen and to promote tissue repair following injury. Due to the strong type 2 immune responses induced by helminths, which can promote tissue repair in the damaged epithelium, their use has been suggested as a possible treatment for inflammatory bowel disease (IBD); however, the role of type 2 immune responses in the initiation and progression of IBD is not fully understood. In this review, we discuss the molecular and cellular mechanisms that regulate type 2 immune responses during intestinal homeostasis, and we briefly discuss the scarce evidence linking type 2 immune responses with the aetiology of IBD.

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