Journal Article

DZNE-2021-01473

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png TREM2-dependent lipid droplet biogenesis in phagocytes is required for remyelination.

Gouna, G. (First author)DZNE* ; Klose, C. ; Bosch-Queralt, M.DZNE* ; Liu, L. ; Gökce, O.Extern* ; Schifferer, M.DZNE* ; Cantuti-Castelvetri, L. (Last author)DZNE* ; Simons, M. (Last author)DZNE*

2021
Rockefeller Univ. Press New York, NY

This record in other databases:    

Please use a persistent id in citations: doi:10.1084/jem.20210227

Abstract: Upon demyelinating injury, microglia orchestrate a regenerative response that promotes myelin repair, thereby restoring rapid signal propagation and protecting axons from further damage. Whereas the essential phagocytic function of microglia for remyelination is well known, the underlying metabolic pathways required for myelin debris clearance are poorly understood. Here, we show that cholesterol esterification in male mouse microglia/macrophages is a necessary adaptive response to myelin debris uptake and required for the generation of lipid droplets upon demyelinating injury. When lipid droplet biogenesis is defective, innate immune cells do not resolve, and the regenerative response fails. We found that triggering receptor expressed on myeloid cells 2 (TREM2)-deficient mice are unable to adapt to excess cholesterol exposure, form fewer lipid droplets, and build up endoplasmic reticulum (ER) stress. Alleviating ER stress in TREM2-deficient mice restores lipid droplet biogenesis and resolves the innate immune response. Thus, we conclude that TREM2-dependent formation of lipid droplets constitute a protective response required for remyelination to occur.

Keyword(s): Animals (MeSH) ; Cholesterol: metabolism (MeSH) ; Endoplasmic Reticulum Stress (MeSH) ; Esterification (MeSH) ; Lipid Droplets: metabolism (MeSH) ; Membrane Glycoproteins: genetics (MeSH) ; Membrane Glycoproteins: metabolism (MeSH) ; Mice, Inbred C57BL (MeSH) ; Mice, Knockout (MeSH) ; Microglia: metabolism (MeSH) ; Microglia: pathology (MeSH) ; Phagocytes: physiology (MeSH) ; Protein Biosynthesis: physiology (MeSH) ; Receptors, Immunologic: genetics (MeSH) ; Receptors, Immunologic: metabolism (MeSH) ; Remyelination: physiology (MeSH) ; Sterol O-Acyltransferase: genetics (MeSH)

---

Contributing Institute(s):

1. Molecular Neurobiology (AG Simons)
2. Molecular Neurodegeneration (AG Haass)
3. Neuronal Cell Biology (AG Misgeld)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)
2. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2021

---

Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Essential Science Indicators ; IF >= 15 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---