{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T19:40:37Z","timestamp":1793907637510,"version":"4.8.0"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,2,4]],"date-time":"2020-02-04T00:00:00Z","timestamp":1580774400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Genetic associations imply a role for <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8+ T cells and the interleukin\u201023 (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201023)\/<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017 axis in psoriatic arthritis (PsA) and other spondyloarthritides (SpA). <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017A+<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8+ (Tc17) T cells are enriched in the synovial fluid (<jats:styled-content style=\"fixed-case\">SF<\/jats:styled-content>) of patients with PsA, and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017A blockade is clinically efficacious in PsA\/SpA. This study was undertaken to determine the immunophenotype, molecular profile, and function of synovial Tc17 cells in order to elucidate their role in PsA\/SpA pathogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Peripheral blood (<jats:styled-content style=\"fixed-case\">PB<\/jats:styled-content>) and <jats:styled-content style=\"fixed-case\">SF<\/jats:styled-content> mononuclear cells were isolated from patients with PsA or other types of SpA. Cells were phenotypically, transcriptionally, and functionally analyzed by flow cytometry (n = 6\u201318), T cell receptor \u03b2 (<jats:styled-content style=\"fixed-case\">TCR<\/jats:styled-content>\u03b2) sequencing (n = 3), <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\u2010Seq (n = 3), quantitative reverse transcriptase\u2013polymerase chain reaction (n = 4), and Luminex or enzyme\u2010linked immunosorbent assay (n = 4\u201316).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u201017A+<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>8+ T cells were predominantly <jats:styled-content style=\"fixed-case\">TCR<\/jats:styled-content>\u03b1\u03b2+ and their frequencies were increased in the <jats:styled-content style=\"fixed-case\">SF<\/jats:styled-content> versus the <jats:styled-content style=\"fixed-case\">PB<\/jats:styled-content> of patients with established PsA (<jats:italic>P<\/jats:italic> &lt; 0.0001) or other SpA (<jats:italic>P<\/jats:italic> = 0.0009). <jats:styled-content style=\"fixed-case\">TCR<\/jats:styled-content>\u03b2 sequencing showed that these cells were polyclonal in PsA (median clonality 0.08), while <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\u2010Seq and deep immunophenotyping revealed that PsA synovial Tc17 cells had hallmarks of Th17 cells (<jats:italic><jats:styled-content style=\"fixed-case\">RORC<\/jats:styled-content><\/jats:italic>\/<jats:italic><jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content><\/jats:italic>23R\/<jats:italic><jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>6<\/jats:italic>\/<jats:italic><jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>161<\/jats:italic>) and Tc1 cells (granzyme A\/B). Synovial Tc17 cells showed a strong tissue\u2010resident memory T (Trm) cell signature and secreted a range of proinflammatory cytokines. We identified <jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>6 as a marker for synovial Tc17 cells, and increased levels of <jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>6 ligand <jats:styled-content style=\"fixed-case\">CXCL<\/jats:styled-content>16 in PsA <jats:styled-content style=\"fixed-case\">SF<\/jats:styled-content> (<jats:italic>P<\/jats:italic> = 0.0005), which may contribute to their retention in the joint.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results identify synovial Tc17 cells as a polyclonal subset of Trm cells characterized by polyfunctional, proinflammatory mediator production and <jats:styled-content style=\"fixed-case\">CXCR<\/jats:styled-content>6 expression. The molecular signature and functional profiling of these cells may help explain how Tc17 cells can contribute to synovial inflammation and disease persistence in PsA and possibly other types of SpA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41156","type":"journal-article","created":{"date-parts":[[2019,11,2]],"date-time":"2019-11-02T10:24:41Z","timestamp":1572690281000},"page":"435-447","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":124,"title":["Polyfunctional, Proinflammatory, Tissue\u2010Resident Memory Phenotype and Function of Synovial Interleukin\u201017A+<scp>CD<\/scp>8+ T Cells in Psoriatic Arthritis"],"prefix":"10.1002","volume":"72","author":[{"given":"Kathryn J. 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