{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:23:52Z","timestamp":1787239432947,"version":"build-2736575974"},"reference-count":51,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,4,30]],"date-time":"2023-04-30T00:00:00Z","timestamp":1682812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002456","name":"Chonnam National University","doi-asserted-by":"publisher","award":["2020\u20101764"],"award-info":[{"award-number":["2020\u20101764"]}],"id":[{"id":"10.13039\/501100002456","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102021R1A6A1A03038899"],"award-info":[{"award-number":["NRF\u20102021R1A6A1A03038899"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102021R1I1A3047818"],"award-info":[{"award-number":["NRF\u20102021R1I1A3047818"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102022M3A9D3016848"],"award-info":[{"award-number":["NRF\u20102022M3A9D3016848"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102022R1C1C1012634"],"award-info":[{"award-number":["NRF\u20102022R1C1C1012634"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To demonstrate the immune landscape of blood and synovial cells in the setting of ankylosing spondylitis (AS) through the analysis of both single\u2010cell transcriptome and surface protein expression, and to unveil the molecular characteristics of pathogenic Th17 cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study included 40 individuals with active AS, 20 individuals with stable AS, 40 patients with active rheumatoid arthritis, and 20 healthy controls. Surface phenotype and intracellular staining were assessed using flow cytometry after peripheral blood mononuclear cells and synovial fluid mononuclear cells were stimulated with T cell receptor. Single\u2010cell transcriptomes of 6 patients with active AS were studied along with cellular indexing of transcriptomes and epitopes by sequencing. We also assessed the outcome of targeting OX40 and glucocorticoid\u2010induced tumor necrosis factor receptor (GITR) on the surface of Th17 cells in a mouse model of curdlan\u2010injected SKG mice in which anti\u2010GITR ligand and\/or anti\u2010OX40 ligand were used.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified pathogenic Th17 cells as polyfunctional interleukin\u201017A (IL\u201017A)\u2013 and interferon\u2010\u03b3 (IFN\u03b3)\u2013producing memory CD4+ T cells, with clinically supportive evidence for their pathogenic roles at sites of inflammation in AS. Transcriptome and flow cytometric analyses revealed that the coexpression of\n                      <jats:italic>TNFRSF4<\/jats:italic>\n                      (OX40) and\n                      <jats:italic>TNFRSF18<\/jats:italic>\n                      (GITR) is increased in pathogenic Th17 cells. Suppression of ligand receptor interactions in vivo through OX40 and GITR effectively suppressed clinical arthritis and decreased pathogenic Th17 cells in the curdlan\u2010injected SKG mouse model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our results have implications for the understanding of pathogenic Th17 cells in AS patients and suggest potential therapeutic targets.<\/jats:p>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art42476-toc-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.42476","type":"journal-article","created":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T10:27:54Z","timestamp":1676370474000},"page":"1176-1186","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Analysis of\n                    <scp>Single\u2010Cell<\/scp>\n                    Transcriptome and Surface Protein Expression in Ankylosing Spondylitis Identifies\n                    <scp>OX40<\/scp>\n                    \u2010Positive and\n                    <scp>Glucocorticoid\u2010Induced<\/scp>\n                    Tumor Necrosis Factor Receptor\u2013Positive Pathogenic Th17 Cells"],"prefix":"10.1002","volume":"75","author":[{"given":"Kijong","family":"Yi","sequence":"first","affiliation":[{"name":"Genome Insight  San Diego 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