Enhanced medullary and extramedullary granulopoiesis sustain the inflammatory response in lupus nephritis
Objectives 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 disord...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2024-03-01
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| Series: | Lupus Science and Medicine |
| Online Access: | https://lupus.bmj.com/content/11/1/e001110.full |
| _version_ | 1797265348129456128 |
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| author | Dimitrios T Boumpas Maria Grigoriou Aggelos Banos Anastasia Filia Pavlos Pavlidis Ioannis Mitroulis Jörn Walter Stavros A Doumas Eleni Zervopoulou Danae Yiannakou Gilles Gasparoni Harikleia Gakiopoulou |
| author_facet | Dimitrios T Boumpas Maria Grigoriou Aggelos Banos Anastasia Filia Pavlos Pavlidis Ioannis Mitroulis Jörn Walter Stavros A Doumas Eleni Zervopoulou Danae Yiannakou Gilles Gasparoni Harikleia Gakiopoulou |
| author_sort | Dimitrios T Boumpas |
| collection | DOAJ |
| description | Objectives 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.Methods 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 β-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.Results Transcriptomic analysis shows that splenic HSPCs carry a higher inflammatory potential compared with their BM counterparts. Further induction of TI, through β-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.Conclusions 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. |
| first_indexed | 2024-04-25T00:43:22Z |
| format | Article |
| id | doaj.art-b3e3c3cc7ee7474a801181662f20c7ee |
| institution | Directory Open Access Journal |
| issn | 2053-8790 |
| language | English |
| last_indexed | 2024-04-25T00:43:22Z |
| publishDate | 2024-03-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Lupus Science and Medicine |
| spelling | doaj.art-b3e3c3cc7ee7474a801181662f20c7ee2024-03-12T07:45:07ZengBMJ Publishing GroupLupus Science and Medicine2053-87902024-03-0111110.1136/lupus-2023-001110Enhanced medullary and extramedullary granulopoiesis sustain the inflammatory response in lupus nephritisDimitrios T Boumpas0Maria Grigoriou1Aggelos Banos2Anastasia Filia3Pavlos Pavlidis4Ioannis Mitroulis5Jörn Walter6Stavros A Doumas7Eleni Zervopoulou8Danae Yiannakou9Gilles Gasparoni10Harikleia Gakiopoulou11Medicine, National and Kapodistrian University of Athens, Athens, Greece1 Laboratory of Autoimmunity and Inflammation, Biomedical Research Foundation of the Academy of Athens, Athens, Greece1 Laboratory of Autoimmunity and Inflammation, Biomedical Research Foundation of the Academy of Athens, Athens, Greece1 Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece3 Institute of Computer Science, Foundation of Research and Technology Hellas, Heraklion, Greece7 Department of Hematology and Laboratory of Molecular Hematology, Department of Medicine, Democritus University of Thrace, Alexandroupolis, GreeceDepartment of Genetics, University of Saarland, Saarbrücken, Germany1 Laboratory of Autoimmunity and Inflammation, Biomedical Research Foundation of the Academy of Athens, Athens, GreeceAutoimmunity and Inflammation Laboratory, Center of Clinical, Experimental Surgery & Translational Research, Biomedical Research Foundation Academy of Athens, Athens, GreeceInstitute of Computer Science, Foundation of Research and Technology Hellas, Heraklion, GreeceDepartment of Genetics-Epigenetics, Saarland University, Saarbrucken, Germany1st Department of Pathology, Medical School, National and Kapodistrian University of Athens, Athens, GreeceObjectives 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.Methods 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 β-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.Results Transcriptomic analysis shows that splenic HSPCs carry a higher inflammatory potential compared with their BM counterparts. Further induction of TI, through β-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.Conclusions 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.https://lupus.bmj.com/content/11/1/e001110.full |
| spellingShingle | Dimitrios T Boumpas Maria Grigoriou Aggelos Banos Anastasia Filia Pavlos Pavlidis Ioannis Mitroulis Jörn Walter Stavros A Doumas Eleni Zervopoulou Danae Yiannakou Gilles Gasparoni Harikleia Gakiopoulou Enhanced medullary and extramedullary granulopoiesis sustain the inflammatory response in lupus nephritis Lupus Science and Medicine |
| title | Enhanced medullary and extramedullary granulopoiesis sustain the inflammatory response in lupus nephritis |
| title_full | Enhanced medullary and extramedullary granulopoiesis sustain the inflammatory response in lupus nephritis |
| title_fullStr | Enhanced medullary and extramedullary granulopoiesis sustain the inflammatory response in lupus nephritis |
| title_full_unstemmed | Enhanced medullary and extramedullary granulopoiesis sustain the inflammatory response in lupus nephritis |
| title_short | Enhanced medullary and extramedullary granulopoiesis sustain the inflammatory response in lupus nephritis |
| title_sort | enhanced medullary and extramedullary granulopoiesis sustain the inflammatory response in lupus nephritis |
| url | https://lupus.bmj.com/content/11/1/e001110.full |
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