IL-23 in inflammatory bowel diseases and colon cancer
- Cytokine Growth Factor Rev. 2019 Feb;45:1-8. doi: 10.1016/j.cytogfr.2018.12.002.
- 1. Department of Medicine 1, University of Erlangen-Nürnberg, Kussmaul Research Campus & Ludwig Demling Endoscopy Center of Excellence, Erlangen, Germany; Deutsches Zentrum für Immuntherapie (DZI), University of Erlangen-Nürnberg, Germany. Electronic address: [email protected].
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.