{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T19:30:19Z","timestamp":1790278219562,"version":"4.1.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T00:00:00Z","timestamp":1763078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015661","name":"UCB Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Although IL-17F is important in psoriasis, the rudimentary biology of IL-17F in the human enthesis remains undefined. We aimed to characterise IL-23-dependent and independent IL-17F production from entheseal innate and adaptive T cells and determine the impact of IL-17F on entheseal stromal function and mesenchymal stem cell (MSC) osteogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Anti-CD3 and anti-CD28 activated human spinal entheseal T cells were immunophenotyped using multi-parameter flow cytometry and a 36-marker Cytometry by Time-Of-Flight (CyTOF) with cytokine profiling, including IL-17A, IL-17F, and TNF (n = 10). IL-17A, IL-17F, and TNF stimulation of entheseal MSC stromal function was evaluated using RNA-seq and by measuring CCL20 protein expression following stimulation with TNF in combination with IL-17A or IL-17F. The osteogenic effects of IL-17A and IL-17F on MSC differentiation were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Inducible IL-17A and IL-17F expression was predominantly from CD4 T cells and CD4+CD25+ T cells, with higher levels of IL-17F at 72 hr. IL-23 significantly increased IL-17F (p \u2264 0.0001) but not IL-17A. Either IL-17A or IL-17F in combination with TNF dramatically upregulated CCL20 protein expression and substantially changed entheseal stromal transcriptome, with differences in gene expression and pathway activation seen between IL-17A or IL-17F stimulation. However, entheseal MSC osteogenesis was not significantly changed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>There was differential induction of IL-17A and IL-17F from innate and adaptive entheseal T cells, with further significant IL-17F augmentation by IL-23, but not IL-17A. Furthermore, the synergistic effects of IL-17A or IL-17F and TNF on stromal function provide the basis for further enthesis IL-17F biology interrogation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1658325","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T07:05:02Z","timestamp":1763103902000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Human spinal enthesis comparative biology of IL-17F and IL-17A reveals greater T-cell IL-17F induction and IL-23 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