{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:55:46Z","timestamp":1789707346586,"version":"4.0.1"},"reference-count":28,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,3,28]],"date-time":"2014-03-28T00:00:00Z","timestamp":1395964800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Innovative Medicines Initiative Joint Undertaking (BTCure project)","award":["115142-2"],"award-info":[{"award-number":["115142-2"]}]},{"DOI":"10.13039\/100004319","name":"Pfizer Inc.","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The cytokine interleukin\u201021 (IL\u201021) can have both proinflammatory and immunosuppressive effects. The purpose of this study was to investigate the potential dual role of IL\u201021 in experimental arthritis in relation to Th17 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Antigen\u2010induced arthritis (AIA) and chronic streptococcal cell wall (SCW) arthritis were induced in IL\u201021 receptor\u2013deficient (IL\u201021R<jats:sup>\u2212\/\u2212<\/jats:sup>) and wild\u2010type mice. Knee joints, synovial tissue, and serum were analyzed for arthritis pathology and inflammatory markers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>During AIA and chronic SCW arthritis, IL\u201021R deficiency protected against severe inflammation and joint destruction. This was accompanied by suppressed serum IgG1 levels and antigen\u2010specific T cell responses. Levels of IL\u201017 were reduced during AIA, and synovial lymphocytes isolated during SCW arthritis for flow cytometry demonstrated that mainly IL\u201017+ interferon\u2010\u03b3 (IFN\u03b3)\u2013positive T cells were reduced in IL\u201021R<jats:sup>\u2212\/\u2212<\/jats:sup> mice. However, during the acute phases of SCW arthritis, significantly higher joint swelling scores were observed, consistent with enhanced tumor necrosis factor and IL\u20106 expression. Interestingly, IL\u201021R<jats:sup>\u2212\/\u2212<\/jats:sup> mice were significantly less capable of up\u2010regulating suppressor of cytokine signaling 1 (SOCS\u20101) and SOCS\u20103 messenger RNA. IL\u201021 stimulation also affected the Toll\u2010like receptor 2 (TLR\u20102)\/caspase recruitment domain 15 response to SCW fragments in vitro, indicating that impaired SOCS regulation in the absence of IL\u201021 signaling might contribute to the increased local activation during SCW arthritis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In contrast to the proinflammatory role of IL\u201021 in adaptive immunity, which drives IL\u201017+IFN+ cells and joint pathology during chronic experimental arthritis, IL\u201021 also has an important immunosuppressive role, presumably by inhibiting TLR signaling via SOCS\u20101 and SOCS\u20103. If this dual role of IL\u201021 in various immune processes is present in human disease, it could make IL\u201021 a difficult therapeutic target in rheumatoid arthritis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38312","type":"journal-article","created":{"date-parts":[[2013,12,10]],"date-time":"2013-12-10T14:48:45Z","timestamp":1386686925000},"page":"886-895","source":"Crossref","is-referenced-by-count":25,"title":["Interleukin\u201021 Receptor Deficiency Increases the Initial Toll\u2010like Receptor 2 Response but Protects Against Joint Pathology by Reducing Th1 and Th17 Cells During Streptococcal Cell Wall Arthritis"],"prefix":"10.1002","volume":"66","author":[{"given":"Renoud J.","family":"Marijnissen","sequence":"first","affiliation":[{"name":"Radboud University Nijmegen Medical Centre Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debbie M.","family":"Roeleveld","sequence":"additional","affiliation":[{"name":"Radboud University Nijmegen Medical Centre Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Young","sequence":"additional","affiliation":[{"name":"Pfizer Inc. Cambridge Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl","family":"Nickerson\u2010Nutter","sequence":"additional","affiliation":[{"name":"Pfizer Inc. Cambridge Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahla","family":"Abdollahi\u2010Roodsaz","sequence":"additional","affiliation":[{"name":"Radboud University Nijmegen Medical Centre Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Garcia de Aquino","sequence":"additional","affiliation":[{"name":"Radboud University Nijmegen Medical Centre Nijmegen The Netherlands"},{"name":"University of S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fons A. J.","family":"van de Loo","sequence":"additional","affiliation":[{"name":"Radboud University Nijmegen Medical Centre Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemiek B.","family":"van Spriel","sequence":"additional","affiliation":[{"name":"Radboud University Nijmegen Medical Centre Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemieke M. H.","family":"Boots","sequence":"additional","affiliation":[{"name":"NV Organon Oss The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim B.","family":"van den Berg","sequence":"additional","affiliation":[{"name":"Radboud University Nijmegen Medical Centre Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marije I.","family":"Koenders","sequence":"additional","affiliation":[{"name":"Radboud University Nijmegen Medical Centre Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,3,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3431"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30418"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.34352"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/35040504"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1077002"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.12.7867"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.9.5886"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.06.001"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05969"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05970"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07021"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0804358105"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.33390"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.20218"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.2006.01795.x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22452"},{"key":"e_1_2_9_18_1","first-page":"139","article-title":"Streptococcal cell wall\u2010induced arthritis and flare\u2010up reaction in mice induced by homologous or heterologous cell walls","volume":"133","author":"den Broek MF","year":"1988","journal-title":"Am J Pathol"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2094"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa035075"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2006.058529"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.02.012"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)62961-6"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21537"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0804350"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.11.6145"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23152"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1630"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0905503"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.38312","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.38312","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T15:35:21Z","timestamp":1759937721000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.38312"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,3,28]]},"references-count":28,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2014,4]]}},"alternative-id":["10.1002\/art.38312"],"URL":"https:\/\/doi.org\/10.1002\/art.38312","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,3,28]]}}}