{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:42:27Z","timestamp":1793148147215,"version":"4.5.0"},"reference-count":115,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Beh\u00e7et\u2019s 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\u2014such as interferon gamma (IFN\u03b3) and tumor necrosis factor alpha (TNF\u03b1)\u2014reflects 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 Beh\u00e7et\u2019s 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-Beh\u00e7et\u2019s 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.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1761519","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T05:31:46Z","timestamp":1773120706000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["The IL-23\/IL-17 axis in Beh\u00e7et\u2019s syndrome pathogenesis: from immunological perspectives to therapeutic implications"],"prefix":"10.3389","volume":"17","author":[{"given":"Mohammad E.","family":"Naffaa","sequence":"first","affiliation":[{"name":"Rheumatology Unit, Galilee Medical Center","place":["Nahariya, Israel"]},{"name":"Azrieli\u2019s Faculty of Medicine, Bar-Ilan University","place":["Safed, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadi","family":"Hassan","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Galilee Medical Center","place":["Nahariya, Israel"]},{"name":"Azrieli\u2019s Faculty of Medicine, Bar-Ilan University","place":["Safed, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmud","family":"Omar","sequence":"additional","affiliation":[{"name":"Maccabi Healthcare Services","place":["Tel-Aviv, Israel"]},{"name":"Sackler Faculty of Medicine, Tel-Aviv University","place":["Tel-Aviv, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerem","family":"Abacar","sequence":"additional","affiliation":[{"name":"Leeds Institute of Rheumatic and Musculoskeletal Medicine, National Institute for Health and Care Research (NIHR) Research Center, University of Leeds","place":["Leeds, United 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