Skip to main content
ISTH 2023 Main banner
Back

    Poster Networking

    Platelets and Megakaryocytes

    Poster Networking Session

    PB0379 - Study of Megakaryocytes in Systemic Lupus Erythematosus

    Sunday, June 25, 2023
    18:30 – 19:30 ET
    Room: Exhibition
    Background: Systemic lupus erythematosus (SLE) is an autoimmune disease associated with accumulation of autoantibodies and autoantigens in blood and organs. Immune complexes (IC) deposition in organs plays a central role in SLE pathogenesis leading to organ damage and increased risks of cardiovascular disease and thrombosis. In SLE, platelets are activated by IC through activation of Fc receptor IIA (FcyRIIA), an immunoreceptor tyrosine-based activation motif. Mouse platelets lack an IC-recognizing receptor on their surface and in order to study the impact of ICs in SLE, we developed a model of NZBxNZWF1 lupus-prone mice expressing the FcyRIIA transgene. The FcyRIIA expression led to accelerated nephritis and thrombosis and profound changes in platelet transcriptome, including an enriched IFN-regulated genes and dysregulated mitochondrial pathways. Mitochondria regulate numerous inflammatory pathways and dysregulation of mitochondria is implicated in the pathophysiology of SLE.

    Aims: As platelets are anucleate, we hypothesize that changes observed in platelets during SLE reflect alterations that occurred in their mother cells, the megakaryocytes (MK). An SLE-prone environment could reprogram MK into a pro-inflammatory phenotype that plays a significant role in driving SLE pathology.

    Methods: NZBxNZWF1 lupus-prone mice expressing or not the FcyRIIA transgene were used. In vitro experiments were achieved using MK differentiated from bone marrow progenitor cells (Lineage-negative selection ). The effects of SLE-relevant stimuli were assessed on MK energy metabolism and functions. Spatial transcriptomic analyses were performed on bone marrow MK.

    Results: IC deposition was observed in organs from lupus-prone mice, noticeably in close contact with MK. Energy metabolism was altered in MK differentiated from SLE mice or in MK differentiated in an SLE-prone environment. Spatial transcriptomic analyses revealed different gene signature in MK from mouse with SLE, depending on their localization within the bone marrow.

    Conclusion(s): An SLE-prone environment alters bioenergetic functions and gene expressions in bone marrow MK.