{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T09:06:16Z","timestamp":1789635976908,"version":"4.0.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"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>Spondyloarthritis (SpA) encompasses axial SpA\/ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and inflammatory bowel disease-associated arthritis, unified by entheseal inflammation, extra-musculoskeletal manifestations, and a strong but atypical genetic signature. Although SpA lacks the highly specific autoantibodies and immune-complex pathology typical of prototypic autoimmune rheumatic diseases, adaptive immune participation is evident, positioning SpA along an immuno-inflammatory continuum bridging autoimmunity and autoinflammation. The IL-23\/IL-17 axis has provided a powerful framework linking barrier perturbation and tissue stress to neutrophil-rich inflammation and to therapeutic efficacy of cytokine blockade. However, IL-17 is increasingly best viewed as an \u201cecosystem\u201d output generated by multiple lymphocyte lineages, including innate-like cells, under tissue-specific constraints, with partial uncoupling from continuous IL-23 dependence in selected sites and disease stages. These features expose the limits of a linear IL-23\/IL-17 model and help explain therapeutic heterogeneity and the imperfect coupling between inflammation control and osteoproliferative outcomes. In parallel, granulocyte-macrophage colony-stimulating factor (GM-CSF) is emerging as a myeloid amplifier that links lymphocyte activation to durable monocyte and macrophage effector programs, reinforcing cytokine redundancy, including TNF and IL-1 family circuits, and promoting inflammatory \u201clock-in\u201d. We propose a \u201cstage \u00d7 tissue\u201d model in which early IL-23\/IL-17 licensing transitions toward a GM-CSF-licensed, IL-17-dominant, partially IL-23-uncoupled, myeloid lock-in phase. We also discuss biomarker strategies integrating cytokine-module readouts with imaging to support precision trials.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1786912","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T08:51:17Z","timestamp":1789635077000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["From IL-23\/IL-17 to GM-CSF: how is the immuno-inflammatory continuum reshaped in spondyloarthritis?"],"prefix":"10.3389","volume":"17","author":[{"given":"Junliang","family":"Jia","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Suzhou Ninth People\u2019s Hospital, Soochow University","place":["Suzhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Suzhou Ninth People\u2019s Hospital, Soochow University","place":["Suzhou, Jiangsu, 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