Interleukin-23 in IBD pathogenesis and implications for therapeutic intervention

Authors
Sewell, Gavin 
Kaser, Arthur 

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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.

Publication Date
Online Publication Date
Acceptance Date
2022-02-19
Keywords
Journal Title
Journal of Crohn's and Colitis
Journal ISSN
1873-9946
Volume Title
Publisher
Oxford University Press (OUP)
Sponsorship
Wellcome Trust (106260/Z/14/Z)
Academy of Medical Sciences (SGL022\1008)
Wellcome Trust (222497/Z/21/Z)
Academy of Medical Sciences