{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T18:55:12Z","timestamp":1793472912894,"version":"4.5.0"},"reference-count":41,"publisher":"National Academy of Sciences","issue":"33","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,8,17]]},"abstract":"<jats:p>\n                    In several murine models of autoimmune arthritis, Th17 cells are the dominant initiators of inflammation. In human arthritis the majority of IL-17\u2013secreting cells within the joint express a cytokine phenotype intermediate between Th17 and Th1. Here we show that Th17\/1 cells from the joints of children with inflammatory arthritis express high levels of both Th17 and Th1 lineage-specific transcription factors, RORC2 and T-bet. Modeling the generation of Th17\/1 in vitro, we show that Th17 cells \u201cconvert\u201d to Th17\/1 under conditions that mimic the disease site, namely low TGF\u03b2 and high IL-12 levels, whereas Th1 cells cannot convert to Th17. Th17\/1 cells from the inflamed joint share T-cell receptor (TCR) clonality with Th17 cells, suggesting a shared clonal origin between Th17 and Th17\/1 cells in arthritis. Using CD161, a lectin-like receptor that is a marker of human Th17, we show synovial Th17 and Th17\/1 cells, and unexpectedly, a large proportion of Th1 cells express CD161. We provide evidence to support a Th17 origin for Th1 cells expressing CD161.\n                    <jats:italic>In vitro,<\/jats:italic>\n                    Th17 cells that convert to a Th1 phenotype maintain CD161 expression. In the joint CD161+ Th1 cells share features with Th17 cells, with shared TCR clonality, expression of RORC2 and CCR6 and response to IL-23, although they are IL-17 negative. We propose that the Th17 phenotype may be unstable and that Th17 cells may convert to Th17\/1 and Th1 cells in human arthritis. Therefore therapies targeting the induction of Th17 cells could also attenuate Th17\/1 and Th1 effector populations within the inflamed joint.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1003852107","type":"journal-article","created":{"date-parts":[[2010,8,2]],"date-time":"2010-08-02T23:35:49Z","timestamp":1280792149000},"page":"14751-14756","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":402,"title":["Th17 plasticity in human autoimmune arthritis is driven by the inflammatory environment"],"prefix":"10.1073","volume":"107","author":[{"given":"Kiran","family":"Nistala","sequence":"first","affiliation":[{"name":"Rheumatology Unit, University College London Institute of Child Health, London, WC1N 1EH, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"Adams","sequence":"additional","affiliation":[{"name":"Great Ormond Street Hospital, London, WC1N 3JH, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Cambrook","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, University College London Institute of Child Health, London, WC1N 1EH, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Ursu","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, University College London Institute of Child Health, London, WC1N 1EH, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biagio","family":"Olivito","sequence":"additional","affiliation":[{"name":"Anna Meyer Children's Hospital and University of Florence, 50139, Florence, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilco","family":"de Jager","sequence":"additional","affiliation":[{"name":"University Medical Centre, 3508 GA, Utrecht, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie G.","family":"Evans","sequence":"additional","affiliation":[{"name":"Infection and Immunity Division, University College London, London, W1T 4JF, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolando","family":"Cimaz","sequence":"additional","affiliation":[{"name":"Anna Meyer Children's Hospital and University of Florence, 50139, Florence, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Bajaj-Elliott","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Microbiology Unit, University College London Institute of Child Health, London, WC1N 1EH, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy R.","family":"Wedderburn","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, University College London Institute of Child Health, London, WC1N 1EH, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,8,2]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132710"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030896"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)00070-4"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1610"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1035999100"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.10.6435"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.23291"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.23655"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2007.080341"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1261"},{"key":"e_1_3_3_11_2","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.4049\/jimmunol.162.3.1246","article-title":"IL-17 is produced by some proinflammatory Th1\/Th0 cells but not by Th2 cells","volume":"162","author":"Aarvak T","year":"1999","unstructured":"T Aarvak, M Chabaud, P Miossec, JB Natvig, IL-17 is produced by some proinflammatory Th1\/Th0 cells but not by Th2 cells. 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