{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T21:49:23Z","timestamp":1790113763667,"version":"4.0.1"},"reference-count":49,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T00:00:00Z","timestamp":1656979200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB969 project C01"],"award-info":[{"award-number":["SFB969 project C01"]}],"id":[{"id":"10.13039\/501100001659","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":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Polymyositis (PM) is a chronic autoimmune inflammatory myopathy resulting in muscle weakness. The limited approved therapies and their poor efficacy contribute to its comorbidity. We investigated the therapeutic use of ONX 0914 and KZR\u2010616, selective inhibitors of the immunoproteasome, in C protein\u2010induced myositis (CIM), a mouse model of PM that closely resembles the human disease. Diseased mice (day 13 postimmunization) were treated with 10 mg\/kg ONX 0914, KZR\u2010616, or vehicle on alternate days until day 28. Endpoints included muscle strength assessed by a grip strength meter, serum creatine kinase activity, histology, and immunohistochemistry analysis. Treatment with ONX 0914 or KZR\u2010616 prevented the loss of grip strength in mice after CIM induction, while vehicle\u2010treated animals displayed progressive muscle weakness. Immunoproteasome inhibition lowered PM\u2010associated leukocyte infiltration of the muscle and prevented increased serum creatine kinase levels. LMP7\u2010deficient mice were resistant to CIM induction, as they showed no alterations in grip strength or creatine kinase (CK) levels or muscular alterations. In conclusion, selective inhibition of the immunoproteasome displays therapeutic efficacy in a preclinical mouse model of PM with suppression of muscle inflammation and preservation of muscle strength. Positive results from this study support the rationale for using KZR\u2010616 in clinical studies.<\/jats:p>","DOI":"10.1002\/eji.202249851","type":"journal-article","created":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T01:52:22Z","timestamp":1655949142000},"page":"1510-1522","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Effective therapy of polymyositis in mice via selective inhibition of the immunoproteasome"],"prefix":"10.1002","volume":"52","author":[{"given":"Marta","family":"del Rio Oliva","sequence":"first","affiliation":[{"name":"Division of Immunology, Department of Biology University of Konstanz Konstanz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J","family":"Kirk","sequence":"additional","affiliation":[{"name":"Kezar Life Sciences South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5423-6399","authenticated-orcid":false,"given":"Marcus","family":"Groettrup","sequence":"additional","affiliation":[{"name":"Division of Immunology, Department of Biology University of Konstanz Konstanz Germany"},{"name":"Biotechnology Institute Thurgau University of Konstanz Kreuzlingen Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9428-2349","authenticated-orcid":false,"given":"Michael","family":"Basler","sequence":"additional","affiliation":[{"name":"Division of Immunology, Department of Biology University of Konstanz Konstanz Germany"},{"name":"Biotechnology Institute Thurgau University of Konstanz Kreuzlingen Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,7,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)14368-1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncl.2014.04.007"},{"key":"e_1_2_9_4_1","first-page":"3984","article-title":"Comparative immunoprofiling of polymyositis and dermatomyositis muscles","volume":"11","author":"Huang K.","year":"2018","journal-title":"Int J Clin Exp Pathol"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410230111"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2012.10.017"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-005-1164-z"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22521"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2016.08.004"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(94)90462-6"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.12.030"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901596"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-397863-9.00003-1"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201846512"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2687"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1978"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b01201"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-47389-w"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209292200"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2015.02.008"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118398"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.2590"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.6.3772"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2017.03.001"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410160206"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830250930"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0104048"},{"key":"e_1_2_9_28_1","first-page":"2045","article-title":"Circulating proteasomes are markers of cell damage and immunologic activity in autoimmune diseases","volume":"29","author":"Egerer K.","year":"2002","journal-title":"J. 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