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Extramedullary hematopoiesis and immune training drive systemic inflammation and associated organ damage in Systemic Lupus Erythematosus

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE218780 | GEO | 2024/03/20

REPOSITORIES: GEO

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Extramedullary hematopoiesis and immune training drive systemic inflammation and associated organ damage in Systemic Lupus Erythematosus (RRBS)

Project description:Extramedullary hematopoiesis (EMH) is an emerging player in peripheral tissue injury in autoimmune disorders. Here, we use the NZBW/F1 lupus mouse model to explore the contribution of EMH to disease pathogenesis of SLE. We demonstrate that EMH takes place in the spleen of F1-L mice and show it is correlated with the activity of lupus nephritis (LN). Transcriptomic analysis demonstrated that splenic hematopoietic stem and progenitor cells (HSPC) carry a higher inflammatory potential than their bone marrow counterparts. Administration of β-glucan, an inducer of innate immunity, exacerbated splenic EMH, increased neutrophil production and worsened LN. Transcriptomic signatures of HSPCs in SLE patients with high disease activity show changes similar to the ones observed in the lupus-prone mouse model. Overall, EMH and trained immunity are ubiquitous in SLE, contributing to disease pathogenesis by sustaining and amplifying the inflammatory response and increasing the risk for flare of the disease.

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