Figure 6.
Autoinflammatory disease caused by aberrant cytokine signaling. Osteoclast and macrophage differentiation is controlled by the cytokines M-CSF and RANKL. Dominantly inherited mutations in SH3BP2 alter the signals that normally come from these cytokines, which results in the differentiation of hyperactive osteoclasts and macrophages that can cause the autoinflammatory disease cherubism. Excess TNF-α produced by these hyperactive macrophages could also feed back through the stroma to increase M-CSF and RANKL levels, although this is still hypothetical.