{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:50:44Z","timestamp":1753869044836,"version":"3.41.2"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:00:00Z","timestamp":1739232000000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2022R1I1A2065168","2019R1A2C1005988"],"award-info":[{"award-number":["2022R1I1A2065168","2019R1A2C1005988"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The inflammatory response triggered by Toll\u2010like receptors (TLRs) may implicated in the development of the pathogenesis of adult\u2010onset Still's disease (AOSD). This study evaluated the efficacy of TLR inhibitor peptides, specifically TLR inhibitor peptide 1 (TIP\u20101) and MAL\/MyD88 inhibitory peptide 2 (MIP\u20102) in animal models of AOSD. THP\u20101 cells were stimulated with TLR agonists and treated with TIP\u20101 or MIP\u20102. Interferon (IFN)\u2010\u03b3 knock\u2010out mice were induced with AOSD\u2010like symptoms using <jats:italic>Mycobacterium<\/jats:italic> mixed with Freund's complete adjuvant (CFA), then treated with the peptides. THP\u20101 cells treated with TIP\u20101 and MIP\u20102 showed significantly decreased expression of TLRs agonist\u2010induced MyD88 and phosphorylated NF\u2010\u03baB, except TLR9 agonists. Furthermore, the peptides resulted in a significant decrease in the concentrations of interleukin (IL)\u20101\u03b2 and IL\u20106 in the culture supernatants, except TLR9 agonists. In animal models of AOSD, treatment with inhibitor peptides significantly improved their clinical symptoms. The administration of these peptides resulted in a significant decrease in serum levels of IL\u20101\u03b2 and IL\u201018. The expression of inflammatory cytokines were downregulated in the spleen and lymph node of TIP\u20101 and MIP\u20102 treated mice. These findings suggest that TIP\u20101 and MIP\u20102 may be effective candidates for AOSD treatment, as they have broad specificity for TLRs.<\/jats:p>","DOI":"10.1002\/eji.202451227","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T09:26:55Z","timestamp":1739266015000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Toll\u2010Like Receptor Blockage by TIP\u20101 and MIP\u20102 Treatment Mitigates Inflammation in a Mouse Model of Adult\u2010Onset Still's Disease or Still's Disease"],"prefix":"10.1002","volume":"55","author":[{"given":"Mi\u2010Hyun","family":"Ahn","sequence":"first","affiliation":[{"name":"Department of Rheumatology Ajou University School of Medicine  Suwon South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang Seon","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Molecular Science and Technology Ajou University  Suwon South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang\u2010Won","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Ajou University School of Medicine  Suwon South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sangdun","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Molecular Science and Technology Ajou University  Suwon South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2609-3367","authenticated-orcid":false,"given":"Hyoun\u2010Ah","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Ajou University School of Medicine  Suwon South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,2,11]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2016.05.010"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-020-05266-2"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.583513"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-019-00762-3"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2017.10.004"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-020-00540-4"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17081342"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.140651"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737159.2019.1615449"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2023.109846"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34560-7"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1900510"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38359"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00461"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06246"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.2174\/138945012803530260"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3713"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2020.119974"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2015.12.018"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2020.102645"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222312764"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9071648"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar4193"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-14004-4"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12969-020-0398-2"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-015-0723-1"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.40727"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.170438"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.181058"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.563335"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-022-02999-1"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.864995"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22041627"},{"key":"e_1_2_11_35_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-019-0244-0","article-title":"A Cell\u2010penetrating Peptide Blocks Toll\u2010Like Receptor\u2010mediated Downstream Signaling and Ameliorates Autoimmune and Inflammatory Diseases in Mice","volume":"51","author":"Kwon H. K.","year":"2019","journal-title":"Experimental & Molecular Medicine"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-021-00676-w"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308496101"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-021-09188-2"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.142.11.8511"}],"container-title":["European Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.202451227","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T04:30:05Z","timestamp":1745814605000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/eji.202451227"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":38,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1002\/eji.202451227"],"URL":"https:\/\/doi.org\/10.1002\/eji.202451227","archive":["Portico"],"relation":{},"ISSN":["0014-2980","1521-4141"],"issn-type":[{"type":"print","value":"0014-2980"},{"type":"electronic","value":"1521-4141"}],"subject":[],"published":{"date-parts":[[2025,2]]},"assertion":[{"value":"2024-04-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202451227"}}