{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T03:17:51Z","timestamp":1790306271357,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T00:00:00Z","timestamp":1696377600000},"content-version":"vor","delay-in-days":276,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001779","name":"Monash University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001779","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008717","name":"Sylvia and Charles Viertel Charitable Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008717","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp; Trans Imm"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      B cells drive the production of autoreactive antibody\u2010secreting cells (ASCs) in autoimmune diseases such as Systemic Lupus Erythematosus (SLE) and Sj\u00f6gren's syndrome, causing long\u2010term organ damage. Current treatments for antibody\u2010mediated autoimmune diseases target B cells or broadly suppress the immune system. However, pre\u2010existing long\u2010lived ASCs are often refractory to treatment, leaving a reservoir of autoreactive cells that continue to produce antibodies. Therefore, the development of novel treatment methods targeting ASCs is vital to improve patient outcomes. Our objective was to test whether targeting the epigenetic regulator BMI\u20101 could deplete ASCs in autoimmune conditions\n                      <jats:italic>in vivo<\/jats:italic>\n                      and\n                      <jats:italic>in vitro<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Use of a BMI\u20101 inhibitor in both mouse and human autoimmune settings was investigated.\n                      <jats:italic>Lyn<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      mice, a model of SLE, were treated with the BMI\u20101 small molecule inhibitor PTC\u2010028, before assessment of ASCs, serum antibody and immune complexes. To examine human ASC survival, a novel human fibroblast\u2010based assay was established, and the impact of PTC\u2010028 on ASCs derived from Sj\u00f6gren's syndrome patients was evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      BMI\u20101 inhibition significantly decreased splenic and bone marrow ASCs in\n                      <jats:italic>Lyn<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>\u2212\/\u2212<\/jats:italic>\n                      <\/jats:sup>\n                      mice. The decline in ASCs was linked to aberrant cell cycle gene expression and led to a significant decrease in serum IgG3, immune complexes and anti\u2010DNA IgG. PTC\u2010028 was also efficacious in reducing\n                      <jats:italic>ex vivo<\/jats:italic>\n                      plasma cell survival from both Sj\u00f6gren's syndrome patients and age\u2010matched healthy donors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These data provide evidence that inhibiting BMI\u20101 can deplete ASC in a variety of contexts and thus BMI\u20101 is a viable therapeutic target for antibody\u2010mediated autoimmune diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cti2.1470","type":"journal-article","created":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T14:58:05Z","timestamp":1696517885000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Targeting BMI\u20101 to deplete antibody\u2010secreting cells in autoimmunity"],"prefix":"10.1002","volume":"12","author":[{"given":"Jack","family":"Polmear","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Monash University  Clayton VIC Australia"},{"name":"Immunity Program, Biomedicine Discovery Institute Monash University  Clayton VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Hailes","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Monash University  Clayton VIC Australia"},{"name":"Immunity Program, Biomedicine Discovery Institute Monash University  Clayton VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moshe","family":"Olshansky","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Monash University  Clayton VIC Australia"},{"name":"Immunity Program, Biomedicine Discovery Institute Monash University  Clayton VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen","family":"Rischmueller","sequence":"additional","affiliation":[{"name":"The Queen Elizabeth Hospital and Basil Hetzel Institute  Woodville South SA Australia"},{"name":"Adelaide Medical School University of Adelaide  Adelaide SA Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elan","family":"L'Estrange\u2010Stranieri","sequence":"additional","affiliation":[{"name":"Department of Immunology, Alfred Research Alliance Monash University  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne L","family":"Fletcher","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Monash University  Clayton VIC Australia"},{"name":"Immunity Program, Biomedicine Discovery Institute Monash University  Clayton VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3751-6751","authenticated-orcid":false,"given":"Margaret L","family":"Hibbs","sequence":"additional","affiliation":[{"name":"Department of Immunology, Alfred Research Alliance Monash University  Melbourne VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa L","family":"Bryant","sequence":"additional","affiliation":[{"name":"Immunology Division Walter &amp; Eliza Hall Institute  Parkville VIC Australia"},{"name":"Department of Medical Biology University of Melbourne  Parkville VIC Australia"},{"name":"Department of Clinical Immunology &amp; Allergy The Royal Melbourne Hospital  Parkville VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1891-7274","authenticated-orcid":false,"given":"Kim L","family":"Good\u2010Jacobson","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Monash University  Clayton VIC Australia"},{"name":"Immunity Program, Biomedicine Discovery Institute Monash University  Clayton VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,10,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-021-00668-1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013010026"},{"key":"e_1_2_9_4_1","first-page":"247","article-title":"The epidemiology of Sjogren's syndrome","volume":"6","author":"Patel R","year":"2014","journal-title":"Clin Epidemiol"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/key332"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-021-00605-2"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1001074107"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2017.11.013"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2012.05.010"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2006.08.016"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201847492"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108504"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2013.04.011"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-01077-y"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI70626"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1402485111"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/bfgp\/ell030"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(22)00277-7"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.00194"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1800137"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1701470"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-10-3161"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90171-X"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200737293"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901878"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-17-0574"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.1.361"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2012.06.003"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200420800"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/16476"},{"key":"e_1_2_9_31_1","first-page":"49","article-title":"Bmi1 overexpression in the cerebellar granule cell lineage of mice affects cell proliferation and survival without initiating medulloblastoma formation","volume":"6","author":"Behesti H","year":"2013","journal-title":"Dis Model Mech"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.21111"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2443.2004.00705.x"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.2010.02475.x"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.42422"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2019-215089"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/mr\/roac007"},{"key":"e_1_2_9_38_1","first-page":"10","article-title":"One year in review 2020: Comorbidities, diagnosis and treatment of primary Sjogren's syndrome","volume":"38","author":"Manfre V","year":"2020","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_9_39_1","first-page":"217","article-title":"B cell depletion with rituximab in the treatment of primary Sjogren's syndrome: What have we learnt?","volume":"37","author":"Grigoriadou S","year":"2019","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2005.12.002"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.16595"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-8411(89)90013-9"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01096"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-01-380121"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep30938"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/1745-6150-7-3"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.098251"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2021.10.020"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw523"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2005046"}],"container-title":["Clinical &amp; Translational Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cti2.1470","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,13]],"date-time":"2024-01-13T20:55:43Z","timestamp":1705179343000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cti2.1470"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1]]},"references-count":50,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2023,1]]}},"alternative-id":["10.1002\/cti2.1470"],"URL":"https:\/\/doi.org\/10.1002\/cti2.1470","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.07.27.550912","asserted-by":"object"}]},"ISSN":["2050-0068","2050-0068"],"issn-type":[{"value":"2050-0068","type":"print"},{"value":"2050-0068","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1]]},"assertion":[{"value":"2023-07-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1470"}}