Section C Project C03

Innate immune training-mediated regulation of osteoclasts and inflammatory bone loss

Trained innate immunity defines that certain stimuli, including diseaseassociated molecular patterns, such as fungal-derived cell wall components, or vaccines, may alter the state of innate immune cells and importantly of their long-lived progenitors in the bone marrow, in such a way, that they are more “prepared” to respond against secondary heterologous stimuli. Trained immunity is associated with enhanced pro-inflammatory cytokine signaling and thus may affect osteoclastogenesis as well. We will analyze whether trained immunity may also affect osteoclast generation and function and how this might contribute to inflammatory bone loss. The overarching theme and long-term perspective of C03 is to show that diseases related to inflammatory bone loss are associated with “trained” bone-marrow progenitors, poised towards enhanced osteoclastogenesis and hence identify trained immunity- associated therapeutic targets.