{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:41:14Z","timestamp":1790959274773,"version":"4.1.0"},"reference-count":40,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T00:00:00Z","timestamp":1710201600000},"content-version":"unspecified","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["742390"],"award-info":[{"award-number":["742390"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013209","name":"Hellenic Foundation for Research and Innovation","doi-asserted-by":"publisher","award":["452"],"award-info":[{"award-number":["452"]}],"id":[{"id":"10.13039\/501100013209","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003448","name":"General Secretariat for Research and Technology","doi-asserted-by":"publisher","award":["\u03a42EDK-02288"],"award-info":[{"award-number":["\u03a42EDK-02288"]}],"id":[{"id":"10.13039\/501100003448","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Lupus Sci Med"],"accepted":{"date-parts":[[2024,2,20]]},"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>In SLE, deregulation of haematopoiesis is characterised by inflammatory priming and myeloid skewing of haematopoietic stem and progenitor cells (HSPCs). We sought to investigate the role of extramedullary haematopoiesis (EMH) as a key player for tissue injury in systemic autoimmune disorders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Transcriptomic analysis of bone marrow (BM)-derived HSPCs from patients with SLE and NZBW\/F1 lupus-prone mice was performed in combination with DNA methylation profile. Trained immunity (TI) was induced through \u03b2-glucan administration to the NZBW\/F1 lupus-prone model. Disease activity was assessed through lupus nephritis (LN) histological grading. Colony-forming unit assay and adoptive cell transfer were used to assess HSPCs functionalities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Transcriptomic analysis shows that splenic HSPCs carry a higher inflammatory potential compared with their BM counterparts. Further induction of TI, through \u03b2-glucan administration, exacerbates splenic EMH, accentuates myeloid skewing and worsens LN. Methylomic analysis of BM-derived HSPCs demonstrates myeloid skewing which is in part driven by epigenetic tinkering. Importantly, transcriptomic analysis of human SLE BM-derived HSPCs demonstrates similar findings to those observed in diseased mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These data support a key role of granulocytes derived from primed HSPCs both at medullary and extramedullary sites in the pathogenesis of LN. EMH and TI contribute to SLE by sustaining the systemic inflammatory response and increasing the risk for flare.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/lupus-2023-001110","type":"journal-article","created":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T02:55:16Z","timestamp":1710212116000},"page":"e001110","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":18,"title":["Enhanced medullary and extramedullary granulopoiesis sustain the inflammatory response in lupus nephritis"],"prefix":"10.1136","volume":"11","author":[{"given":"Eleni","family":"Zervopoulou","sequence":"first","affiliation":[{"name":"Autoimmunity and Inflammation Laboratory, Center of Clinical, Experimental Surgery & Translational Research, Biomedical Research Foundation Academy of Athens, Athens, Greece"},{"name":"4th Department of Internal Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, 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