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The IL-23/Th17 Axis in Intestinal Inflammation

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Molecular Genetics of Inflammatory Bowel Disease

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Abstract

Over the past 5 years, a wealth of data has emerged from experimental models linking the IL-23/Th17 axis with chronic intestinal inflammation. Clinical studies have also reported elevated levels of IL-23 and Th17 cytokines in the inflamed intestine of IBD patients, and recent genome-wide association studies (GWAS) have associated polymorphisms in IL23R, and in other Th17-related genes, with susceptibility to IBD. However, the precise mechanisms through which the IL-23/Th17 axis contributes to intestinal homeostasis are not fully understood. Recent studies have revealed that IL-23 drives intestinal inflammation by stimulating conserved effector responses, characterized by the production of IL-17A, IFN-γ and IL-22, from several populations of innate and adaptive intestinal leukocytes. However, the effects of individual Th17 cytokines are complex, ranging from disease-protective to highly pathogenic, and are governed by the context in which they are expressed and by the presence of additional factors in the intestine. More recently, it has been shown that distinct members of the intestinal microbiota can modulate the Th17 axis and can regulate the balance between Th17 and Treg cells in the intestine. In addition, several approaches using pharmacological or biological inhibitors of the IL-23/Th17 axis have been demonstrated to alleviate autoimmune pathology. These findings suggest that strategies targeting the IL-23/Th17 axis could constitute novel therapies for IBD. However, a better understanding of how the IL-23/Th17 axis interacts with host genetic factors and the intestinal microbiota in the normal and diseased intestine is necessary to ensure that these novel therapies are applied to appropriate patient cohorts.

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Acknowledgements

The author would like to acknowledge The Wellcome Trust and CRUK for research grants support and George Song-Zhao for help with preparing the figure.

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  1. Sir William Dunn School of Pathology, University of Oxford, Oxford, UK

    Kevin J. Maloy

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  1. Gastroenterology unit, Patient Area Gastroenterology, Dermatovenereology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden

    Charlotte Hedin

  2. Montreal Heart Institute and Université de Montréal, Montréal, QC, Canada

    John D. Rioux

  3. School of Biological Sciences, Monash University, Clayton, VIC, Australia

    Mauro D'Amato

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Maloy, K.J. (2019). The IL-23/Th17 Axis in Intestinal Inflammation. In: Hedin, C., Rioux, J., D'Amato, M. (eds) Molecular Genetics of Inflammatory Bowel Disease. Springer, Cham. https://doi.org/10.1007/978-3-030-28703-0_13

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