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.
|Tatsächlicher Beginn/ -es Ende||01.01.10 → 31.12.14|
2015 einigten sich UN-Mitgliedstaaten auf 17 globale Ziele für nachhaltige Entwicklung (Sustainable Development Goals, SDGs) zur Beendigung der Armut, zum Schutz des Planeten und zur Förderung des allgemeinen Wohlstands. Die Arbeit dieses Projekts leistet einen Beitrag zu folgendem(n) SDG(s):