TU Dresden


Osteoimmunology - Previous and Current Research

Intercellular communications within the bone microenvironment

Our previous work addressed the interplay of cell signaling pathways during lymphoid development in the thymus (αβ vs. γδ T lineage decision), as well as the developmental plasticity of bone marrow derived precursor cells (Garbe et al., 2006; Kreslavsky et al., 2008; Krueger et al., 2006). Our recent studies also include the skeletal system and with this focus on the interaction of bone and immune system.

Bone provides a microenvironment that is essential for the development of hematopoietic stem cells (HSC), which give rise to all cells of the immune system. Homeostasis of this microenvironment critically depends on bone remodeling, a process tightly regulated by bone-forming osteoblasts and bone-resorbing osteoclasts, which is in addition crucial to maintain a healthy bone structure in order to avoid diseases such as osteoporosis or osteopetrosis. Reciprocally, increasing evidence exists that immune cells exert profound effects on bone, e.g. under inflammatory conditions such as rheumatoid arthritis, where osteoclasts play a pivotal role in the pathogenesis of bone destruction, illustrating the mutual interaction between these two systems. In this context, we have recently shown that the absence of functional Foxp3-expressing regulatory T cells results in severe lympho-hematopoietic defects, which establish during mouse ontogeny (Riewaldt et al., Frontiers Immunol 2012) and provided evidence that a modified cytokine milieu accounts for increased numbers of osteoclasts in a novel mouse model for osteopetrosis (Garbe et al., JBMR 2012). Our overall goal is to decipher molecular and cellular mechanisms to develop novel therapeutic strategies for bone marrow transplantation as well as for bone disorders such as osteoporosis and rheumatoid arthritis.