REVIEW article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders: Autoinflammatory Disorders
This article is part of the Research TopicBehçet’s Syndrome: From Pathophysiology to Personalized TherapeuticsView all articles
The IL-23/IL-17 Axis in Behçet's Syndrome Pathogenesis: From Immunological Perspectives to Therapeutic Implications
Provisionally accepted
- 1Galilee Medical Center, Nahariya, Israel
- 2Bar-Ilan University, Ramat Gan, Israel
- 3Maccabi Healthcare Services, Tel Aviv-Yafo, Israel
- 4Tel Aviv University, Tel Aviv-Yafo, Israel
- 5University of Leeds Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, United Kingdom
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Behçet's Syndrome (BS) is a systemic vasculitis characterized by variable vessel involvement and an elusive etiology, though immunogenetic studies strongly implicate the IL-23/IL-17 axis which bridges innate and adaptive immunity, orchestrating type 17 T-cell responses thus modulating neutrophil function-with this cell a central player in both BS clinical features and immunopathology. Additionally, the contribution of Th1 cytokines—such as interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα)—reflects the broader immune plasticity observed in BS pathophysiology. Despite the immunogenetics incriminating the IL-23/IL-17 axis, clinical evidence confirming the role of IL-23/IL-17/inhibition in BS therapy is still limited including disappointing results with secukinumab in trials for Behçet's uveitis. However, emerging evidence from small-scale retrospective studies, prospective trials, and case reports indicates that IL-23/IL-17 axis inhibition may benefit mucocutaneous and articular manifestations, as well as neuro-Behçet's disease and the licensed PDE4 inhibitor apremilast regulates multiple aspects of IL-23/17 axis and neutrophil biology. Interestingly, anti-IL-17 therapy has been linked to BS induction. Herein, we discuss IL-23/IL-17 axis inhibition in BS and why it should be used cautiously and be limited to mucocutaneous and/or articular manifestations at this juncture. Further randomized controlled trials are imperative to dissect the IL-23/IL-17 axis in BS including high-dose anti-IL-23 therapy antagonism given that neutrophils are an abundant source of IL-23 and consider novel strategies including IL-23R antagonism.
Keywords: Behcet's syndrome, Interleukin 17, interleukin 23, MHC-1-opathy, Pathogenesis
Received: 05 Dec 2025; Accepted: 16 Feb 2026.
Copyright: © 2026 Naffaa, Hassan, Omar, Abacar and McGonagle. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Fadi Hassan
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.