Interleukin-23 in IBD pathogenesis and implications for therapeutic intervention
View / Open Files
Authors
Sewell, Gavin
Kaser, Arthur
Journal Title
Journal of Crohn's and Colitis
ISSN
1873-9946
Publisher
Oxford University Press (OUP)
Type
Article
This Version
AM
Metadata
Show full item recordCitation
Sewell, G., & Kaser, A. Interleukin-23 in IBD pathogenesis and implications for therapeutic
intervention. Journal of Crohn's and Colitis https://doi.org/10.17863/CAM.82070
Abstract
The IL-23 cytokine, derived predominantly from macrophages and dendritic cells in response to microbial stimulation, has emerged as a critical promoter of chronic intestinal inflammation. Genome-wide association studies linking variants in IL-23R to disease protection, bolstered by experimental evidence from colitis models, and the successful application of therapies against the IL-12/IL-23 shared p40 subunit in the treatment of inflammatory bowel disease all provide compelling evidence of a crucial role for IL-23 in disease pathogenesis. Moreover, targeting the p19 subunit specific for IL-23 has shown considerable promise in recent phase 2 studies in inflammatory bowel disease. The relative importance of the diverse immunological pathways downstream of IL-23 in propagating mucosal inflammation in the gut however remains contentious. Here we review current understanding of IL-23 biology and explore its pleiotropic effects on T cells, innate lymphoid, myeloid and intestinal epithelial cells in the context of inflammatory bowel disease pathogenesis. We furthermore discuss these pathways in the light of recent evidence from clinical trials and indicate emerging targets amenable to therapeutic intervention and translation into clinical practice.
Sponsorship
Academy of Medical Sciences
Funder references
Wellcome Trust (106260/Z/14/Z)
Academy of Medical Sciences (SGL022\1008)
Wellcome Trust (222497/Z/21/Z)
Embargo Lift Date
2025-03-03
Identifiers
This record's DOI: https://doi.org/10.17863/CAM.82070
This record's URL: https://www.repository.cam.ac.uk/handle/1810/334652
Statistics
Total file downloads (since January 2020). For more information on metrics see the
IRUS guide.