Submit a Letter to the Editor

TREM2 sustains microglial expansion during aging and response to demyelination
Pietro Luigi Poliani, … , Susan Gilfillan, Marco Colonna
Pietro Luigi Poliani, … , Susan Gilfillan, Marco Colonna
Published April 20, 2015
Citation Information: J Clin Invest. 2015;125(5):2161-2170. https://doi.org/10.1172/JCI77983.
View: Text | PDF
Research Article Neuroscience

TREM2 sustains microglial expansion during aging and response to demyelination

Abstract

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 with an abnormal morphology. In the cuprizone model of oligodendrocyte degeneration and demyelination, Trem2–/– microglia failed to amplify transcripts indicative of activation, phagocytosis, and lipid catabolism in response to myelin damage. As a result, Trem2–/– mice exhibited impaired myelin debris clearance, axonal dystrophy, oligodendrocyte reduction, and persistent demyelination after prolonged cuprizone treatment. Moreover, myelin-associated lipids robustly triggered TREM2 signaling in vitro, suggesting that TREM2 may directly sense lipid components exposed during myelin damage. We conclude that TREM2 is required for promoting microglial expansion during aging and microglial response to insults of the white matter.

Authors

Pietro Luigi Poliani, Yaming Wang, Elena Fontana, Michelle L. Robinette, Yoshinori Yamanishi, Susan Gilfillan, Marco Colonna

×

Guidelines: The Editorial Board will only consider letters that we deem relevant and of interest to our readers. We will not post data that have not been subjected to peer review, nor will we post letters that are essentially a reiteration of another letter. We reserve the right to edit any letter for length, content, and clarity. Authors will be notified by e-mail if their letters were accepted. No appeals will be considered.

Specific requirements: All letters must be 400 words or fewer. You may enter the letter as plain text or HTML. The author's name and e-mail address are required, and will be posted with the letter. All possible conflicts of interest must be noted, even if they are not posted. If you wish to include a figure (keep in mind that non-peer-reviewed data will not be posted), please contact the editors directly at editors@the-jci.org.

This field is required
This field is required
This field is required
This field is required
This field is required

This field is required