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In recent years, the involvement of the interleukin (IL)-23\/IL-17 axis in the pathophysiology of axSpA has been widely proposed. Since IL-23 is an upstream activating cytokine of IL-17, theoretically targeting IL-23 should be effective in axSpA, especially after the success of the treatment with IL-17 blockers in the disorder. Unfortunately, IL-23 blockade did not show meaningful efficacy in clinical trials of AS. In this review, we analyzed the possible causes of the failure of IL-23 blockers in AS: 1) the available data from an animal model is not able to support that IL-23 is involved in a preclinical rather than clinical phase of axSpA; 2) Th17 cells are not principal inflammatory cells in the pathogenesis of axSpA; 3) IL-17 may be produced independently of IL-23 in several immune cell types other than Th17 cells in axSpA; 4) no solid evidence supports IL-23 as a pathogenic factor to induce enthesitis and bone formation. Taken together, IL-23 is not a principal proinflammatory cytokine in the pathogenesis of axSpA.<\/jats:p>","DOI":"10.3389\/fimmu.2022.818413","type":"journal-article","created":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T05:06:36Z","timestamp":1644469596000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["No Significant Effects of IL-23 on Initiating and Perpetuating the Axial Spondyloarthritis: The Reasons for the Failure of IL-23 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