IL-23 in inflammatory bowel diseases and colon cancer. (February 2019)

• Record Type: Journal Article
• Authors: Neurath, Markus F.
• Is Part Of: Cytokine & growth factor reviews. Volume 45(2019)
• Page Start: 1
• Page End: 8
• Publication Date: 2019-02
• Subjects: CD crohn's disease -- UC ulcerative colitis -- IBD inflammatory bowel disease -- CRC colorectal cancer; IBD -- Colon cancer -- Cytokines -- IL-23 -- Immune response; Cytokines -- Periodicals; 571.84
• DOI: 10.1016/j.cytogfr.2018.12.002
• Languages: English
• ISSNs: 1359-6101

Abstract

Graphical abstract: IL-23 controls activation and cytokine production of various immune cells in colitis such as natural killer (NK) cells, intraepithelial lymphocytes (IEL), innate lymphoid cells (ILCs), and T helper 17 cells (Th17). In contrast, IL-23 blocks activation of regulatory T cells (Tr1, Treg). Highlights: IL-23 production is elevated in patients with inflammatory bowel diseases and colon cancer. IL-23 target cells comprise T helper 17 cells, innate lymphoid cells type 3, granulocytes, intraepithelial lymphocytes and natural killer cells. IL-23-induced immune cell activation aggravates gut inflammation and promotes growth of colon cancer. Suppression of IL-23 or IL-23R function led to suppression of mucosal inflammation in various mouse models of colitis. Antibodies against IL-12/IL-23 p40 and IL-23 p19 have been successfully used in clinical trials for therapy of Crohn´s disease. 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.