biostudies-literaturePoliani PLNIA NIH HHSNIDDK NIH HHS2161-70https://www.ebi.ac.uk/biostudies/studies/S-EPMC4463196biostudies-literatureUnknown125(5)Microglia contribute to development, homeostasis, and immunity of the CNS. Like other tissue-resident macrophage populations, microglia express the surface receptor triggering receptor expressed on myeloid cells 2 (TREM2), which binds polyanions, such as dextran sulphate and bacterial LPS, and activates downstream signaling cascades through the adapter DAP12. Individuals homozygous for inactivating mutations in TREM2 exhibit demyelination of subcortical white matter and a lethal early onset dementia known as Nasu-Hakola disease. How TREM2 deficiency mediates demyelination and disease is unknown. Here, we addressed the basis for this genetic association using Trem2(-/-) mice. In WT mice, microglia expanded in the corpus callosum with age, whereas aged Trem2(-/-) mice had fewer microglia witThe Journal of clinical investigationTREM2 sustains microglial expansion during aging and response to demyelination.PMC4463196P60 DK020579DK020579P50 AG005681P30 DK020579P50 AG005681-30Gilfillan SFontana EColonna MWang YRobinette MLYamanishi YPoliani PLfalseTREM2 sustains microglial expansion during aging and response to demyelination.Microglia contribute to development, homeostasis, and immunity of the CNS. Like other tissue-resident macrophage populations, microglia express the surface receptor triggering receptor expressed on myeloid cells 2 (TREM2), which binds polyanions, such as dextran sulphate and bacterial LPS, and activates downstream signaling cascades through the adapter DAP12. Individuals homozygous for inactivating mutations in TREM2 exhibit demyelination of subcortical white matter and a lethal early onset dementia known as Nasu-Hakola disease. How TREM2 deficiency mediates demyelination and disease is unknown. Here, we addressed the basis for this genetic association using Trem2(-/-) mice. In WT mice, microglia expanded in the corpus callosum with age, whereas aged Trem2(-/-) mice had fewer microglia wit2015-01-01T00:00:00Z2015 May2026-05-03T03:21:39.107Z2019-03-27T01:53:15ZS-EPMC44631962589360210.1172/jci7798310.1172/JCI77983