SPP 1468, Subproject: Bone marrow plasma cells in autoimmune lupus modulating the function of bone metabolizing cells - osteoblasts and osteoclasts

    Project: DFG ProjectsDFG Joint Research: Priority Programs

    Project Details

    Description

    Previously, we have shown that long-lived plasma cells home into environmental niches in the bone marrow and that the number of these cells is severely increased in autoimmune systemic lupus erythematosus (SLE). While plasma cell survival is supported within these niches, the dialog between niche and plasma cell seems to be bi-directional. There is increasing evidence that bone marrow plasma cells interact with multiple resident cell types, including osteoblasts and osteoclasts - cells of the bone metabolism. Bone marrow plasma cells produce the cytokine CCL3 (and possibly others) which induces osteoclast activation. CCL3 mediates bone destruction in multiple myeloma bone disease when neoplastic CCL3 producing myeloma plasma cells – resembling the neoplastic counterpart of long-lived bone marrow plasma cells - accumulate in high numbers. For unknown reasons, low bone mineral density is also observed in autoimmune SLE. Here, we propose that via the production of CCL3 and other cytokines, increased numbers of long-lived plasma cells also mediate abnormalities in bone metabolism in this autoimmune disease. We plan to test this hypothesis (I) in chimeric mice containing plasma cells derived from SLE-prone hyperreactive NZM2410 background but wild type osteoblasts and osteoclasts, (II) after specific depletion of long-lived plasma cells via proteasome inhibition in wild type and B cell deficient μMT mice, (III) in plasma cell osteoblast-osteoclast co-cultures in vitro.
    Statusfinished
    Effective start/end date01.01.1031.12.14

    UN Sustainable Development Goals

    In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This project contributes towards the following SDG(s):

    • SDG 3 - Good Health and Well-being

    Research Areas and Centers

    • Academic Focus: Center for Infection and Inflammation Research (ZIEL)

    DFG Research Classification Scheme

    • 205-18 Rheumatology