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ToolsElzubeir, Amera, Patel, Meha and Rushbrook, Simon (2026) The Interleukin-17-T helper 17 axis in primary sclerosing cholangitis: A narrative review of an emerging pathogenic frontier. Autoimmunity Reviews, 25 (8). ISSN 1568-9972
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Abstract
Interleukin-17 (IL-17) and IL-17+ secretory cells, including T helper 17 (Th17) cells play pivotal roles in autoimmune diseases such as psoriasis. Emerging evidence implicates the IL-17 pathway in primary sclerosing cholangitis (PSC), a chronic cholestatic liver disease lacking approved pharmacological therapies, for which liver transplantation remains the only life-extending option. The IL-17 pathway and Th17 biology is increasingly implicated in PSC pathogenesis through its interactions with hepatic parenchymal and non-parenchymal cells, including cholangiocytes, neutrophils and hepatic stellate cells which promote periductal fibro-inflammation, immune cell recruitment and pro-inflammatory cytokine release. Th17 cells and IL-17+ secreting lymphocytes localise to peribiliary regions, exacerbating biliary injury and fibrosis. Preclinical murine models suggest that inhibition of IL-17 signalling mitigates hepatic fibro-inflammatory responses, providing a compelling rationale for its investigation as a potential therapeutic target in PSC.Whilst licensed IL-17 inhibitors have demonstrated efficacy and safety in a number of autoimmune and immune-mediated diseases, IL-17 has context-dependent roles in tissue homeostasis and host defence underscoring the pathway's complexity. This narrative review synthesises the biology of the IL-17 family, integrating preclinical and translational evidence relevant to PSC, and discusses the translational potential of approved anti-IL-17 agents as novel therapeutic candidates in PSC, whilst highlighting key uncertainties and gastrointestinal safety considerations.
| Item Type: | Article |
|---|---|
| Additional Information: | Data availability: All data relevant to the study are included in the article. |
| Uncontrolled Keywords: | cholestatic liver disease,il-17,liver immunology,primary sclerosing cholangitis,t helper 17,immunology and allergy,immunology ,/dk/atira/pure/subjectarea/asjc/2700/2723 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 16 Jul 2026 11:13 |
| Last Modified: | 16 Jul 2026 11:13 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/103886 |
| DOI: | 10.1016/j.autrev.2026.104095 |
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