TREM2 in Regulating Macrophage Inflammatory Responses and Disease Pathogenesis

Abstract

Triggering receptor expressed on myeloid cells 2 (TREM2) is a cell-surface receptor belonging to the TREM family that is predominantly expressed on myeloid cells such as granulocytes, monocytes, osteocytes, macrophages, and microglia. While much of the functionality of TREM2 is not well understood at the molecular level, it is well-established that TREM2 plays a significant role in the regulation of a broad definition of macrophage inflammatory responses. Dysregulation of TREM2 has been implicated in a large number of diseases including Alzheimer’s disease, Nasu-Hakola disease, bone-related diseases, and atherosclerosis. The TREM2 gene is highly conserved evolutionarily and at the level of controlling its expression. The function of TREM2 is highly conserved across the broad definition of macrophages, including microglia, osteoclasts, and vascular macrophages. This genetic and physiological “niche conservatism” strongly suggests its pivotal role in regulating inflammatory responses. This mini-review summarizes our current understanding of the structure, expression, and function of TREM2 in the pathogenesis of macrophage-mediated diseases.