# The IL-23/IL-17 axis in Behçet’s syndrome pathogenesis: from immunological perspectives to therapeutic implications

## TL;DR

This paper explores the role of the IL-23/IL-17 immune pathway in Behçet’s Syndrome and its potential as a treatment target.

## Contribution

The paper highlights the IL-23/IL-17 axis as a key player in Behçet’s Syndrome and suggests cautious use of its inhibition for specific symptoms.

## Key findings

- The IL-23/IL-17 axis is central to Behçet’s Syndrome immunopathology and clinical features.
- Inhibition of the IL-23/IL-17 axis may benefit mucocutaneous and articular manifestations.
- Anti-IL-17 therapy has been linked to inducing Behçet’s Syndrome.

## Abstract

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.