{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T20:13:49Z","timestamp":1792872829276,"version":"4.5.0"},"reference-count":34,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,8,12]],"date-time":"2019-08-12T00:00:00Z","timestamp":1565568000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K23AI108951"],"award-info":[{"award-number":["K23AI108951"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI097134"],"award-info":[{"award-number":["R01AI097134"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012051","name":"Lupus Research Alliance","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012051","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      We previously identified a role for EZH2, a transcriptional regulator in inducing proinflammatory epigenetic changes in lupus CD4+ T cells. This study was undertaken to investigate whether inhibiting EZH2 ameliorates lupus\u2010like disease in MRL\/\n                      <jats:italic>lpr<\/jats:italic>\n                      mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      EZH2 expression levels in multiple cell types in lupus patients were evaluated using flow cytometry and messenger RNA expression data. Inhibition of EZH2 in MRL\/\n                      <jats:italic>lpr<\/jats:italic>\n                      mice was achieved by intraperitoneal 3\u2032\u2010deazaneplanocin (DZNep) administration using a preventative and a therapeutic treatment model. Effects of DZNep on animal survival, anti\u2013double\u2010stranded DNA (anti\u2010dsDNA) antibody production, proteinuria, renal histopathology, cytokine production, and T and B cell numbers and percentages were assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      EZH2 expression levels were increased in whole blood, neutrophils, monocytes, B cells, and CD4+ T cells in lupus patients. In MRL\/\n                      <jats:italic>lpr<\/jats:italic>\n                      mice, inhibition of EZH2 by DZNep was confirmed by significant reduction of EZH2 and H3K27me3 in splenocytes. Inhibiting EZH2 with DZNep treatment before or after disease onset improved survival and significantly reduced anti\u2010dsDNA antibody production. DZNep\u2010treated mice displayed a significant reduction in renal involvement, splenomegaly, and lymphadenopathy. Lymphoproliferation and numbers of double\u2010negative T cells were significantly reduced in DZNep\u2010treated mice. Concentrations of circulating cytokines and chemokines, including tumor necrosis factor, interferon\u2010\u03b3, CCL2, RANTES\/CCL5, interleukin\u201010 (IL\u201010), keratinocyte\u2010derived chemokine\/CXCL1, IL\u201012, IL\u201012p40, and CCL4\/macrophage inflammatory protein 1\u03b2, were decreased in DZNep\u2010treated mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      EZH2 is up\u2010regulated in multiple cell types in lupus patients. Therapeutic inhibition of EZH2 abrogates lupus\u2010like disease in MRL\/\n                      <jats:italic>lpr<\/jats:italic>\n                      mice, suggesting that EZH2 inhibitors may be repurposed as a novel therapeutic option for lupus patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.40931","type":"journal-article","created":{"date-parts":[[2019,5,20]],"date-time":"2019-05-20T07:06:06Z","timestamp":1558335966000},"page":"1681-1690","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Inhibition of EZH2 Ameliorates Lupus\u2010Like Disease in MRL\/\n                    <i>lpr<\/i>\n                    Mice"],"prefix":"10.1002","volume":"71","author":[{"given":"Dallas M.","family":"Rohraff","sequence":"first","affiliation":[{"name":"University of Michigan  Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"He","sequence":"additional","affiliation":[{"name":"University of Michigan, Ann Arbor, and the Second Xiangya Hospital and Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan A.","family":"Farkash","sequence":"additional","affiliation":[{"name":"University of Michigan  Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Schonfeld","sequence":"additional","affiliation":[{"name":"University of Michigan  Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei\u2010Suen","family":"Tsou","sequence":"additional","affiliation":[{"name":"University of Michigan  Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3884-962X","authenticated-orcid":false,"given":"Amr 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