{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T05:26:03Z","timestamp":1777353963050,"version":"3.51.4"},"reference-count":45,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2011,10,21]],"date-time":"2011-10-21T00:00:00Z","timestamp":1319155200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["FEBS Letters"],"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:p>A hypomorphic mutation of the gene encoding zeta\u2010associated protein\u201070 (ZAP\u201070), a signaling molecule in T cells, produces autoimmune arthritis in mice under a microbially conventional condition but not in a clean environment. The genetic anomaly alters thymic selection of self\u2010reactive T cells as well as natural regulatory T cells and their respective functions. Highly self\u2010reactive polyclonal T cells, including arthritogenic ones, thus produced by the thymus strongly recognize self\u2010antigens presented by antigen\u2010presenting cells, stimulate them to up\u2010regulate co\u2010stimulatory molecules and secrete cytokines that drive na\u00efve self\u2010reactive T cells to differentiate into autoimmune effector Th17 cells. Administration of microbial products and activation of complement can facilitate the differentiation, evoking clinically overt arthritis in a microbially clean environment. Furthermore, mutation\u2010dependent graded attenuation of T cell receptor signaling alters disease phenotypes and the dependency of disease occurrence on the environment. These findings provide a model of how genetic and environmental factors, in association, cause autoimmune diseases such as rheumatoid arthritis.<\/jats:p>","DOI":"10.1016\/j.febslet.2011.10.026","type":"journal-article","created":{"date-parts":[[2011,10,26]],"date-time":"2011-10-26T01:16:41Z","timestamp":1319591801000},"page":"3633-3639","source":"Crossref","is-referenced-by-count":18,"title":["Thymus, innate immunity and autoimmune arthritis: Interplay of gene and environment"],"prefix":"10.1002","volume":"585","author":[{"given":"Shimon","family":"Sakaguchi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshinaga","family":"Ito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinji","family":"Maeda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noriko","family":"Sakaguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Motomu","family":"Hashimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,10,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2005.09.006"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.21.120601.141122"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.25.022106.141532"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90598-7"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02119"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200421795"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20041758"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.21.120601.141107"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000848"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20062259"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/10.12.1969"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071397"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20092301"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132710"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80442-2"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.11.013"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20082902"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2007.07.018"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/376435a0"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90368-9"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8202713"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8202712"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.182.4.1057"},{"key":"e_1_2_9_25_1","first-page":"34515","article-title":"Temperature-sensitive ZAP70 mutants degrading through a proteasome-independent pathway","volume":"70","author":"Matsuda S.","year":"1999","journal-title":"Biochemistry"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.1.656"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2001.01246.x"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200939385"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-008-0718-x"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.163.5.2610"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.178.5.1701"},{"key":"e_1_2_9_32_1","unstructured":"E.D. Harris 1997 WB Saunders Philadelphia"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxn091"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.155.3.1151"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.184.2.387"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1086\/422827"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1323"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1086\/423790"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-1108"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21049"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05911"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1673"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M600498200"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20041982"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.bor.0000160780.13012.be"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002281-200205000-00011"}],"container-title":["FEBS Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1016%2Fj.febslet.2011.10.026","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1016%2Fj.febslet.2011.10.026","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1016\/j.febslet.2011.10.026","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T19:13:54Z","timestamp":1694978034000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1016\/j.febslet.2011.10.026"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,10,21]]},"references-count":45,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2011,12]]}},"alternative-id":["10.1016\/j.febslet.2011.10.026"],"URL":"https:\/\/doi.org\/10.1016\/j.febslet.2011.10.026","archive":["Portico"],"relation":{},"ISSN":["0014-5793","1873-3468"],"issn-type":[{"value":"0014-5793","type":"print"},{"value":"1873-3468","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,10,21]]}}}