{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T15:46:47Z","timestamp":1791733607641,"version":"4.3.4"},"reference-count":58,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFC2702003"],"award-info":[{"award-number":["2021YFC2702003"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Systemic juvenile idiopathic arthritis (sJIA) is a chronic arthritis characterized primarily by systemic inflammatory responses. However, its pathogenesis remains incompletely understood and may be related to the activation of Toll\u2010like receptors (TLRs). To overcome limitations of existing models, this study develops an animal model mimicking sJIA systemic inflammatory features via TLR4 activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We integrated multi\u2010center single\u2010cell and bulk RNA\u2010seq data from sJIA patients and healthy children to assess TLR pathway activity. Based on the analysis of differentially expressed TLR molecules, we identified TLR4 as an important factor. A chronic arthritis mouse model (LC) was constructed by introducing sustained TLR4 activation into the collagen\u2010induced arthritis (CIA) model. The general condition, inflammation, and joint pathology were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In sJIA patients, TLR pathway activation, particularly in monocytes, was identified as a key feature. Bulk RNA\u2010seq analysis revealed TLR4 expression was significantly upregulated in sJIA. The LC mouse model exhibited pronounced systemic inflammation, including fever, weight loss, splenomegaly, and elevated inflammatory cytokines (IL\u201018, TNF\u2010\u03b1, IFN\u2010\u03b3). Immunofluorescence confirmed significant CD163\n                      <jats:sup>+<\/jats:sup>\n                      macrophage infiltration in the liver of LC mice. Interestingly, despite the exacerbated systemic inflammation, the LC mice exhibited milder joint damage, lower arthritis scores, and less cartilage degradation compared to the CIA group, demonstrating a dissociation between systemic inflammation and joint pathology.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study identifies sustained TLR4 activation as a critical driver of systemic inflammation in sJIA. The LC model effectively recapitulates systemic features of sJIA while revealing a dissociation between systemic inflammation and joint damage.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ame2.70290","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:10:11Z","timestamp":1790241011000},"page":"1795-1812","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Construction and evaluation of a chronic arthritis animal model induced by persistent activation of toll\u2010like receptors via lipopolysaccharide stimulation"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7226-6565","authenticated-orcid":false,"given":"Fengming","family":"Li","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology Children's Hospital of Chongqing Medical University  Chongqing China"},{"name":"Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity Children's Hospital of Chongqing Medical University  Chongqing China"},{"name":"National Clinical Research Center for Children and Adolescents' Health and Diseases, Children's Hospital of Chongqing Medical University  Chongqing China"},{"name":"Ministry of Education Key Laboratory of Child Development and Disorders Children's Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7613-916X","authenticated-orcid":false,"given":"Qiang","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology Children's Hospital of Chongqing Medical University  Chongqing China"},{"name":"Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity Children's Hospital of Chongqing Medical University  Chongqing China"},{"name":"National Clinical Research Center for Children and Adolescents' Health and Diseases, Children's Hospital of Chongqing Medical University  Chongqing China"},{"name":"Ministry of Education Key Laboratory of Child Development and Disorders Children's Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinglin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology Children's Hospital of Chongqing Medical University  Chongqing China"},{"name":"Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity Children's Hospital of Chongqing Medical University  Chongqing China"},{"name":"National Clinical Research Center for Children and Adolescents' Health and Diseases, Children's Hospital of Chongqing Medical University  Chongqing China"},{"name":"Ministry of Education Key Laboratory of Child Development and Disorders Children's Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology Children's Hospital of Chongqing Medical University  Chongqing China"},{"name":"Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity Children's Hospital of Chongqing Medical University  Chongqing China"},{"name":"National Clinical Research Center for Children and Adolescents' Health and Diseases, Children's Hospital of Chongqing Medical University  Chongqing China"},{"name":"Ministry of Education Key Laboratory of Child Development and Disorders Children's Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9656-0296","authenticated-orcid":false,"given":"Xuemei","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology Children's Hospital of Chongqing Medical University  Chongqing China"},{"name":"Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity Children's Hospital of Chongqing Medical University  Chongqing China"},{"name":"National Clinical Research Center for Children and Adolescents' Health and Diseases, Children's Hospital of Chongqing Medical University  Chongqing China"},{"name":"Ministry of Education Key Laboratory of Child Development and Disorders Children's Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60363-8"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60244-4"},{"issue":"10","key":"e_1_2_13_4_1","first-page":"1991","article-title":"Revision of the proposed classification criteria for juvenile idiopathic arthritis: Durban, 1997","volume":"25","author":"Petty RE","year":"1998","journal-title":"J Rheumatol"},{"issue":"2","key":"e_1_2_13_5_1","first-page":"390","article-title":"International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001","volume":"31","author":"Petty RE","year":"2004","journal-title":"J Rheumatol"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-210324"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2011.68"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2016.07.004"},{"issue":"6","key":"e_1_2_13_9_1","first-page":"459","article-title":"The incidence of macrophage activation syndrome in children with rheumatic disorders","volume":"63","author":"Moradinejad MH","year":"2011","journal-title":"Minerva Pediatr"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.100655"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-023-03032-8"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1916"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.02.041"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00461"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.09.051"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-200598"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2024-225853"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12969-021-00660-9"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1638"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1003893107"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.583513"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00182"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5396.2085"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2008.09.011"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.241786"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA117.001322"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-025-03606-8"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4463"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2021.06.043"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200006)30:6<1568::AID-IMMU1568>3.0.CO;2-R"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.173"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI43157"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2015.04.018"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0285-6"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20170412"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2011.12.008"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22157960"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02995"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830260716"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.159.11.5687"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2015.12.011"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.shk.0000142249.08135.e9"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.52.3.315"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1089\/jir.1995.15.387"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.3.783"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2006.26.682"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1684-1182(10)60027-8"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-005-0138-5"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.24953\/turkjped.2019.06.005"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2009.09.010"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keu524"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0107886"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.17305\/bjbms.2021.6016"},{"key":"e_1_2_13_55_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1800765"},{"key":"e_1_2_13_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22416"},{"key":"e_1_2_13_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-024-02011-8"},{"key":"e_1_2_13_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1471-1"},{"key":"e_1_2_13_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/d41586-019-02340-x"}],"container-title":["Animal Models and Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ame2.70290","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ame2.70290","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ame2.70290","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T15:24:51Z","timestamp":1791732291000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ame2.70290"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":58,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/ame2.70290"],"URL":"https:\/\/doi.org\/10.1002\/ame2.70290","archive":["Portico"],"relation":{},"ISSN":["2576-2095","2576-2095"],"issn-type":[{"value":"2576-2095","type":"print"},{"value":"2576-2095","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2026-03-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}