{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T21:13:53Z","timestamp":1774991633304,"version":"3.50.1"},"reference-count":29,"publisher":"Proceedings of the National Academy of Sciences","issue":"10","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,5,13]]},"abstract":"<jats:p>\n            IL-17 is a T cell-derived, proinflammatory cytokine that is suspected to be involved in the development of various inflammatory diseases. Although there are elevated levels of IL-17 in synovial fluid of patients with rheumatoid arthritis, the pathogenic role of IL-17 in the development of rheumatoid arthritis remains to be elucidated. In this report, the effects of IL-17 deficiency were examined in IL-1 receptor antagonist-deficient (IL-1Ra\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            ) mice that spontaneously develop an inflammatory and destructive arthritis due to unopposed excess IL-1 signaling. IL-17 expression is greatly enhanced in IL-1Ra\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice, suggesting that IL-17 activity is involved in the pathogenesis of arthritis in these mice. Indeed, the spontaneous development of arthritis did not occur in IL-1Ra\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice also deficient in IL-17. The proliferative response of ovalbumin-specific T cells from DO11.10 mice against ovalbumin cocultured with antigen-presenting cells from either IL-1Ra\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice or wild-type mice was reduced by IL-17 deficiency, indicating insufficient T cell activation. Cross-linking OX40, a cosignaling molecule on CD4\n            <jats:sup>+<\/jats:sup>\n            T cells that plays an important role in T cell antigen-presenting cell interaction, with anti-OX40 Ab accelerated the production of IL-17 induced by CD3 stimulation. Because OX40 is induced by IL-1 signaling, IL-17 induction is likely to be downstream of IL-1 through activation of OX40. These observations suggest that IL-17 plays a crucial role in T cell activation, downstream of IL-1, causing the development of autoimmune arthritis.\n          <\/jats:p>","DOI":"10.1073\/pnas.1035999100","type":"journal-article","created":{"date-parts":[[2003,5,13]],"date-time":"2003-05-13T18:28:41Z","timestamp":1052850521000},"page":"5986-5990","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":388,"title":["IL-17 production from activated T cells is required for the spontaneous development of destructive arthritis in mice deficient in IL-1 receptor antagonist"],"prefix":"10.1073","volume":"100","author":[{"given":"Susumu","family":"Nakae","sequence":"first","affiliation":[{"name":"Center for Experimental Medicine and Department of Cancer Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan"}]},{"given":"Shinobu","family":"Saijo","sequence":"additional","affiliation":[{"name":"Center for Experimental Medicine and Department of Cancer Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan"}]},{"given":"Reiko","family":"Horai","sequence":"additional","affiliation":[{"name":"Center for Experimental Medicine and Department of Cancer Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan"}]},{"given":"Katsuko","family":"Sudo","sequence":"additional","affiliation":[{"name":"Center for Experimental Medicine and Department of Cancer Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan"}]},{"given":"Shigeo","family":"Mori","sequence":"additional","affiliation":[{"name":"Center for Experimental Medicine and Department of Cancer Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan"}]},{"given":"Yoichiro","family":"Iwakura","sequence":"additional","affiliation":[{"name":"Center for Experimental Medicine and Department of Cancer Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan"}]}],"member":"341","published-online":{"date-parts":[[2003,4,29]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"5483","volume":"155","author":"Yao Z","year":"1995","unstructured":"Z Yao, S L Painter, W C Fanslow, D Ulrich, B M Macduff, M K Spriggs, R J Armitage J Immunol 155, 5483\u20135486 (1995).","journal-title":"J Immunol"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3109\/08830189809043008"},{"key":"e_1_3_3_3_2","first-page":"3513","volume":"160","author":"Jovanovic D V","year":"1998","unstructured":"D V Jovanovic, J A Di Battista, J Martel-Pelletier, F C Jolicoeur, Y He, M Zhang, F Mineau, J P Pelletier J Immunol 160, 3513\u20133521 (1998).","journal-title":"J Immunol"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.42.27467"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI5703"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2000.00041.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.9.4783"},{"key":"e_1_3_3_8_2","first-page":"3137","volume":"20","author":"Hirahara N","year":"2000","unstructured":"N Hirahara, Y Nio, S Sasaki, M Takamura, C Iguchi, M Dong, K Yamasawa, M Itakura, K Tamura Anticancer Res 20, 3137\u20133142 (2000).","journal-title":"Anticancer Res"},{"key":"e_1_3_3_9_2","first-page":"577","volume":"162","author":"Antonysamy M A","year":"1999","unstructured":"M A Antonysamy, W C Fanslow, F Fu, W Li, S Qian, A B Troutt, A W Thomson J Immunol 162, 577\u2013584 (1999).","journal-title":"J Immunol"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.5.2832"},{"key":"e_1_3_3_11_2","first-page":"1246","volume":"162","author":"Aarvak T","year":"1999","unstructured":"T Aarvak, M Chabaud, P Miossec, J B Natvig J Immunol 162, 1246\u20131251 (1999).","journal-title":"J Immunol"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.2.1004"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.191.2.313"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6101(02)00021-7"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(02)00391-6"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.187.9.1463"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2125367"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.1.90"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10172"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/8.2.275"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1177\/36.1.3275709"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7689748"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199906)42:6<1291::AID-ANR29>3.0.CO;2-#"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200010)30:10<2815::AID-IMMU2815>3.0.CO;2-#"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(01)02127-5"},{"key":"e_1_3_3_26_2","first-page":"6390","volume":"161","author":"Wagner U G","year":"1998","unstructured":"U G Wagner, P J Kurtin, A Wahner, M Brackertz, D J Berry, J J Goronzy, C M Weyand J Immunol 161, 6390\u20136397 (1998).","journal-title":"J Immunol"},{"key":"e_1_3_3_27_2","first-page":"598","volume":"152","author":"Yellin M J","year":"1994","unstructured":"M J Yellin, K Sippel, G Inghirami, L R Covey, J J Lee, J Sinning, E A Clark, L Chess, S Lederman J Immunol 152, 598\u2013608 (1994).","journal-title":"J Immunol"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.1.9"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(95)90070-5"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1035999100","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T23:37:20Z","timestamp":1649806640000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1035999100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,4,29]]},"references-count":29,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2003,5,13]]}},"alternative-id":["10.1073\/pnas.1035999100"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1035999100","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,4,29]]},"assertion":[{"value":"2002-10-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2003-04-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}