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Microglial autophagy-associated phagocytosis is essential for recovery from neuroinflammation
- Source :
- Science immunology, 5(52):eabb5077. American Association for the Advancement of Science, Berglund, R, Guerreiro-Cacais, A O, Adzemovic, M Z, Zeitelhofer, M, Lund, H, Ewing, E, Ruhrmann, S, Nutma, E, Parsa, R, Thessen-Hedreul, M, Amor, S, Harris, R A, Olsson, T & Jagodic, M 2020, ' Microglial autophagy-associated phagocytosis is essential for recovery from neuroinflammation ', Science immunology, vol. 5, no. 52, eabb5077 . https://doi.org/10.1126/sciimmunol.abb5077, Science Immunology
- Publication Year :
- 2020
-
Abstract
- Multiple sclerosis (MS) is a leading cause of incurable progressive disability in young adults caused by inflammation and neurodegeneration in the central nervous system (CNS). The capacity of microglia to clear tissue debris is essential for maintaining and restoring CNS homeostasis. This capacity diminishes with age, and age strongly associates with MS disease progression, although the underlying mechanisms are still largely elusive. Here, we demonstrate that the recovery from CNS inflammation in a murine model of MS is dependent on the ability of microglia to clear tissue debris. Microglia-specific deletion of the autophagy regulator Atg7, but not the canonical macroautophagy protein Ulk1, led to increased intracellular accumulation of phagocytosed myelin and progressive MS-like disease. This impairment correlated with a microglial phenotype previously associated with neurodegenerative pathologies. Moreover, Atg7-deficient microglia showed notable transcriptional and functional similarities to microglia from aged wild-type mice that were also unable to clear myelin and recover from disease. In contrast, induction of autophagy in aged mice using the disaccharide trehalose found in plants and fungi led to functional myelin clearance and disease remission. Our results demonstrate that a noncanonical form of autophagy in microglia is responsible for myelin degradation and clearance leading to recovery from MS-like disease and that boosting this process has a therapeutic potential for age-related neuroinflammatory conditions.
- Subjects :
- 0301 basic medicine
Male
Encephalomyelitis, Autoimmune, Experimental
Multiple Sclerosis
Immunology
Central nervous system
Primary Cell Culture
Inflammation
Biology
Autophagy-Related Protein 7
03 medical and health sciences
Myelin
Mice
0302 clinical medicine
Phagocytosis
medicine
Autophagy
Animals
Autophagy-Related Protein-1 Homolog
Humans
Neuroinflammation
Cells, Cultured
Myelin Sheath
Mice, Knockout
Microglia
Multiple sclerosis
Neurodegeneration
Brain
General Medicine
medicine.disease
Cell biology
030104 developmental biology
medicine.anatomical_structure
Spinal Cord
Female
medicine.symptom
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 24709468
- Database :
- OpenAIRE
- Journal :
- Science immunology, 5(52):eabb5077. American Association for the Advancement of Science, Berglund, R, Guerreiro-Cacais, A O, Adzemovic, M Z, Zeitelhofer, M, Lund, H, Ewing, E, Ruhrmann, S, Nutma, E, Parsa, R, Thessen-Hedreul, M, Amor, S, Harris, R A, Olsson, T & Jagodic, M 2020, ' Microglial autophagy-associated phagocytosis is essential for recovery from neuroinflammation ', Science immunology, vol. 5, no. 52, eabb5077 . https://doi.org/10.1126/sciimmunol.abb5077, Science Immunology
- Accession number :
- edsair.doi.dedup.....64fc8dc9dac85a325d15eed7fcf96dae