{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:20:43Z","timestamp":1790875243922,"version":"4.1.0"},"reference-count":56,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2010,12,28]],"date-time":"2010-12-28T00:00:00Z","timestamp":1293494400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2011,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Both Th1 cells and Th17 cells have been recognized in rheumatoid arthritis (RA); however, it remains unclear whether Th1 cells and\/or Th17 cells are involved in driving disease chronicity and destructiveness. The aim of this study was to identify and characterize the functional role of Th17 cells in early RA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Flow cytometry analysis was performed on peripheral blood mononuclear cells (PBMCs) from treatment\u2010naive patients with early RA and age\u2010matched healthy volunteers. PBMCs from these patients, naive T cells, and primary CCR6\u2212 Th1 cells and CCR6+ Th17 cells were sorted and cultured in the absence or presence of synovial fibroblasts from patients with early RA (RASFs), and cytokine expression and gene transcription were analyzed. In addition, tumor necrosis factor \u03b1 (TNF\u03b1)\u2013 and interleukin\u201017A (IL\u201017A)\u2013blocking experiments were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the PBMCs of treatment\u2010naive patients with early RA, an increased fraction of IL\u201017A\u2013and TNF\u03b1\u2013producing CCR6+ Th17 cells was observed. When cocultured with RASFs, these primary Th17 cells were potent inducers of IL\u20106 and IL\u20108 and the tissue\u2010destructive enzymes matrix metalloproteinase 1 (MMP\u20101) and MMP\u20103, whereas primary Th1 cells or naive T cells were not. Importantly, specific up\u2010regulation of IL\u201017A but not TNF\u03b1 or interferon\u2010\u03b3 was observed in RASF\/Th17 cell cocultures. In addition to TNF\u03b1 blocking, IL\u201017A neutralization was required to further down\u2010regulate Th17 activity in RASF\/Th17 cell cocultures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Th17 cells, but not Th1 cells, cooperated with RASFs in a proinflammatory feedback loop, revealing a potential mechanism by which human Th17 cells drive chronic destructive disease in patients with RA. Furthermore, the neutralization of IL\u201017A activity is essential in current anti\u2010TNF therapies to suppress Th17 cell activity in patients with early RA and potentially other Th17 cell\u2013mediated disorders.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.30093","type":"journal-article","created":{"date-parts":[[2010,10,15]],"date-time":"2010-10-15T18:47:19Z","timestamp":1287168439000},"page":"73-83","source":"Crossref","is-referenced-by-count":296,"title":["Th17 cells, but not Th1 cells, from patients with early rheumatoid arthritis are potent inducers of matrix metalloproteinases and proinflammatory cytokines upon synovial fibroblast interaction, including autocrine interleukin\u201017A production"],"prefix":"10.1002","volume":"63","author":[{"given":"J. P.","family":"van Hamburg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. 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