Figure 3.

A novel hypothesis for the pathogenesis of Nasu-Hakola disease. TREM2/TYROBP, encoding different proteins of the same receptor signaling complex involved in the activation of the immune response, are expressed by osteoclasts, microglia, oligodendrocytes, dendritic cells, macrophages, and granulocytes. On the immune system side, the inactivation of TREM2 or TYROBP may lead to the overproduction of autoantibodies and pro-inflammatory cytokines by macrophages and dendritic cells, a process which is normally restrained by the physiological presence of TREM2 and TYROBP. Finally, the inactivation of TREM2 and TYROBP is reflected in the dysfunction of different bodily systems, including bones, CNS, and (auto)immunity, all sharing a common myeloid progenitor and pointing to Nasu-Hakola disease as a “myeloid cell disease.” autoAbs, autoantibodies.