Article

The IL-23/IL-17 pathway in inflammatory bowel disease

Translational Gastroenterology Unit, Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
Expert review of gastroenterology & hepatology (Impact Factor: 2.42). 04/2012; 6(2):223-37. DOI: 10.1586/egh.11.107
Source: PubMed

ABSTRACT

The etiology of inflammatory bowel disease is unknown but available evidence suggests that a deregulated immune response towards the commensal bacterial flora is responsible for intestinal inflammation in genetically predisposed individuals. IL-23 promotes expansion and maintenance of Th17 cells, which secrete the proinflammatory cytokine IL-17 and have been implicated in the pathogenesis of many chronic inflammatory disorders. Recent studies have shown that IL-23 also acts on cells of the innate immune system that can contribute to inflammatory cytokine production and tissue inflammation. A role for the IL-23/IL-17 pathway in the pathogenesis of chronic intestinal inflammation in inflammatory bowel disease has emerged from both animal and human studies. Here we aim to review the recent advances in this rapidly moving field.

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Available from: Alessandra Geremia, Feb 02, 2016
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    • "Also IL-23, released by macrophages and dendritic cells located in the intestinal mucosa, activates signal transducer and activator of transcription-(STAT-) 4 in memory T lymphocytes, stimulating the production of IFN-í µí»¾. In turn, IFN-í µí»¾ is responsible for triggering the production of inflammatory cytokines in cells of the innate immune system, contributing to the increase of the inflammation present in colitis [35]. Latest results from Neurath group [3] identified a pathogenic role of IL-9 in experimental and human ulcerative colitis by regulating intestinal epithelial cells. "
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    ABSTRACT: Inflammatory bowel diseases (IBD) are characterized by chronic inflammation of the intestinal tract associated with an imbalance of the intestinal microbiota. Crohn’s disease (CD) and ulcerative colitis (UC) are the most widely known types of IBD and have been the focus of attention due to their increasing incidence. Recent studies have pointed out genes associated with IBD susceptibility that, together with environment factors, may contribute to the outcome of the disease. In ulcerative colitis, there are several therapies available, depending on the stage of the disease. Aminosalicylates, corticosteroids, and cyclosporine are used to treat mild, moderate, and severe disease, respectively. In Crohn’s disease, drug choices are dependent on both location and behavior of the disease. Nowadays, advances in treatments for IBD have included biological therapies, based mainly on monoclonal antibodies or fusion proteins, such as anti-TNF drugs. Notwithstanding the high cost involved, these biological therapies show a high index of remission, enabling a significant reduction in cases of surgery and hospitalization. Furthermore, migration inhibitors and new cytokine blockers are also a promising alternative for treating patients with IBD. In this review, an analysis of literature data on biological treatments for IBD is approached, with the main focus on therapies based on emerging recombinant biomolecules.
    Full-text · Dataset · Aug 2015
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    • "Also IL-23, released by macrophages and dendritic cells located in the intestinal mucosa, activates signal transducer and activator of transcription-(STAT-) 4 in memory T lymphocytes, stimulating the production of IFN-í µí»¾. In turn, IFN-í µí»¾ is responsible for triggering the production of inflammatory cytokines in cells of the innate immune system, contributing to the increase of the inflammation present in colitis [35]. Latest results from Neurath group [3] identified a pathogenic role of IL-9 in experimental and human ulcerative colitis by regulating intestinal epithelial cells. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Inflammatory bowel diseases (IBD) are characterized by chronic inflammation of the intestinal tract associated with an imbalance of the intestinal microbiota. Crohn's disease (CD) and ulcerative colitis (UC) are the most widely known types of IBD and have been the focus of attention due to their increasing incidence. Recent studies have pointed out genes associated with IBD susceptibility that, together with environment factors, may contribute to the outcome of the disease. In ulcerative colitis, there are several therapies available, depending on the stage of the disease. Aminosalicylates, corticosteroids, and cyclosporine are used to treat mild, moderate, and severe disease, respectively. In Crohn's disease, drug choices are dependent on both location and behavior of the disease. Nowadays, advances in treatments for IBD have included biological therapies, based mainly on monoclonal antibodies or fusion proteins, such as anti-TNF drugs. Notwithstanding the high cost involved, these biological therapies show a high index of remission, enabling a significant reduction in cases of surgery and hospitalization. Furthermore, migration inhibitors and new cytokine blockers are also a promising alternative for treating patients with IBD. In this review, an analysis of literature data on biological treatments for IBD is approached, with the main focus on therapies based on emerging recombinant biomolecules.
    Full-text · Article · Mar 2015 · Mediators of Inflammation
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    • "IL-21 also induces the expression of the IL-23R [27]. IL-26 is a member of the IL-10 family, which is produced by the activated memory T cells and induces the expression of proinflammatory cytokines, such as TNF-a and IL-8, and inhibits cell proliferation [28]. CCL20 is a ligand for CCR6 and it have an antimicrobial and chemoattractive activities [19]. "
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    ABSTRACT: CD4+ T helper (Th) cells play an important role in modulating immune responses. Th17 cells are a newly established Th subpopulation. Th17 cells differentiate in the presence of TGF-β and IL-6 in mice or IL-1β and IL-6 in humans, depending on the transcription factor RORγt. IL-23 stabilizes the Th17 cells phenotype and helps Th17 cells acquire effector functions. Th17 secretes IL-17, IL-21, and IL-22, which play significant role in the immune response against viruses, extracellular bacteria and fungi, as well as in the pathogenesis of inflammatory diseases. The systemic and local activity of IL-17 and Th17 seems to be an important part of development of autoimmune reaction. Th17 cell subpopulation has been described in many types of cancer, including gastric cancer, melanoma, breast cancer, and ovarian cancer, but it remains unclear whether Th17 cells promote or inhibit tumor progression and the mechanism of their involvement in tumor immunity is unknown. This review summarizes the current knowledge on the role of Th17 cells in tumor immunity.
    Full-text · Article · Apr 2014 · Acta haematologica Polonica
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