IL-23 in inflammatory bowel diseases and colon cancer |
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| Institution: | 1. Department of Medicine 1, University of Erlangen-Nürnberg, Kussmaul Research Campus & Ludwig Demling Endoscopy Center of Excellence, Erlangen, Germany;2. Deutsches Zentrum für Immuntherapie (DZI), University of Erlangen-Nürnberg, Germany;1. Departments of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt;2. Tropical Medicine, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt;3. Clinical Pathology, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt;1. Internal Medicine, Health Radiation Research Department, National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt;2. Clinical Pathology, Health Radiation Research Department, National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt;1. Department of Immunology-Oncology, Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada;2. Département de microbiologie, infectiologie et immunologie, Université de Montréal, Montreal, Quebec H3C 3J7, Canada;3. Departments of Pediatrics, Ophthalmology and Pharmacology, CHU Sainte-Justine Research Centre, Montréal, Canada;4. Department of Pharmacology, Université de Montréal, Montréal, Canada;5. Department of Pharmacology and Therapeutics, McGill University, Montréal, Canada;6. Department of Biochemistry, University of Montreal, Montreal, Quebec H3C 3J7, Canada;7. Montreal Heart Institute, Research Center, 5000 Belanger Street, Montreal, Quebec H1T 1C8, Canada;8. Department of Medicine, Université de Montréal, Montreal, Quebec H3T 1J4, Canada;1. Department of Microbiology & Immunology, Columbia University Irving Medical Center, New York, NY USA;1. Section of Digestive Diseases, Yale University, New Haven, Connecticut;2. Division of Gastroenterology, University of California, San Diego, La Jolla, California;3. Department of Gastroenterology, University Hospital Leuven, Leuven, Belgium |
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| Abstract: | Studies in recent years have identified a pivotal role of the cytokine IL-23 in the pathogenesis of inflammatory bowel diseases (IBD: Crohn´s disease, ulcerative colitis) and colitis-associated colon cancer. Genetic studies revealed that subgroups of IBD patients have single nucleotide polymorphisms in the IL-23R gene suggesting that IL-23R signaling affects disease susceptibility. Furthermore, increased production of IL-23 by macrophages, dendritic cells or granulocytes has been observed in various mouse models of colitis, colitis-associated cancer and IBD patients. Moreover, in several murine models of colitis, suppression of IL-12/IL-23 p40, IL-23 p19 or IL-23R function led to marked suppression of gut inflammation. This finding was associated with reduced activation of IL-23 target cells such as T helper 17 cells, innate lymphoid cells type 3, granulocytes and natural killer cells as well as with impaired production of proinflammatory cytokines. Based on these findings, targeting of IL-23 emerges as important concept for suppression of gut inflammation and inflammation-associated cancer growth. Consistently, neutralizing antibodies against IL-12/IL-23 p40 and IL-23 p19 have been successfully used in clinical trials for therapy of Crohn´s disease and pilot studies in ulcerative colitis are ongoing. These findings underline the crucial regulatory role of IL-23 in chronic intestinal inflammation and colitis-associated cancer and indicate that therapeutic strategies aiming at IL-23 blockade may be of key relevance for future therapy of IBD patients. |
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| Keywords: | IBD Colon cancer Cytokines IL-23 Immune response |
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