Innate immune responses in neurodegeneration
Triggering receptors expressed on myeloid cells (TREM) are cell surface receptors encoded on human chromosome 6 that we found to be differentially expressed on granulocytes, dendritic cells, macrophages, microglia and osteoclasts and regulate their functions. Human deficiency in TREM2 or the associated signaling adaptor DAP12 causes a progressive, early onset dementia known as Nasu-Hakola disease. Recently, a TREM2 polymorphism was implicated as a genetic risk for Alzheimer’s disease (AD). We are currently exploring the capacity of TREM2 to promote microglial cell function and how TREM2 allelic variants result in susceptibility to AD. We also recently demonstrated that the cytokine IL-34 promotes the proliferation and survival of microglia through the receptor CSF-1R. We are testing IL-34 as a therapeutic strategy for neurodegenerative diseases.