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Recent research on TNF has revealed the increased level of transmembrane TNF in the joint tissue of SpA patients compared to that of rheumatoid arthritis patients, which appears to facilitate TNF-driven osteo-proliferative changes in AS. In addition, there is considerable interest in the central role of IL-23\/IL-17 axis in type 3 immunity and the therapeutic potential of blocking this axis to ameliorate enthesitis and NBF in AS. AS immunopathology involves a variety of immune cells, including both innate and adoptive immune cells, to orchestrate the immune response driving type 3 immunity. In response to external stimuli of inflammatory cytokines, local osteo-chondral progenitor cells activate intra-cellular anabolic molecules and signals involving hedgehog, bone morphogenetic proteins, receptor activator of nuclear factor kappa-B ligand, and Wnt pathways to promote NBF in AS. Here, we provide an overview of the current immunopathology and future directions for the treatment of enthesitis and NBF associated with AS.<\/jats:p>","DOI":"10.1093\/mr\/roab057","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T13:17:40Z","timestamp":1633958260000},"page":"484-492","source":"Crossref","is-referenced-by-count":24,"title":["Complexity of enthesitis and new bone formation in ankylosing spondylitis: current understanding of the immunopathology and therapeutic approaches"],"prefix":"10.1093","volume":"32","author":[{"given":"Masaki","family":"Kusuda","sequence":"first","affiliation":[{"name":"Schroeder Arthritis Institute, Krembil Research Institute, University Health Network, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigil","family":"Haroon","sequence":"additional","affiliation":[{"name":"Schroeder Arthritis Institute, Krembil Research Institute, University Health Network, Toronto, ON, 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