Abstract:
:Amyotrophic lateral sclerosis (ALS) is a fatal and progressive neurodegenerative disease affecting predominantly motor neurons in the spinal cord and motor cortex. Neurodegeneration in ALS is accompanied by a well-characterized neuroinflammatory reaction within the central nervous system and, as described more recently, cells of the peripheral immune system. Particularly monocytes have been implicated in ALS pathogenesis. Exosomes are membrane-enclosed vesicles secreted by various cell types with a diameter of 50-150 nm. Circulating blood exosomes have been shown to be important mediators and regulators of immunity. Therefore, we hypothesize that circulating blood exosomes are putative mediators of monocytic deregulation in ALS. Here we characterize exosomal uptake and the respective immunological reaction of peripheral monocytes from ALS patients and healthy donors using both serum-derived exosomes and TDP-43-loaded exosomes produced in cell culture. We found the pro-inflammatory cytokine secretion by ALS monocytes upon exosomal stimulation to be impaired compared with control monocytes. Moreover, we demonstrate that exosomal TDP-43 induces increased monocytic activation compared with non-aggregation-prone cargo. Therefore, this study underlines the functional deregulation of ALS monocytes and the impact of circulating blood exosomes on monocyte activation.
journal_name
Immunol Cell Bioljournal_title
Immunology and cell biologyauthors
Zondler L,Feiler MS,Freischmidt A,Ruf WP,Ludolph AC,Danzer KM,Weishaupt JHdoi
10.1038/icb.2016.89subject
Has Abstractpub_date
2017-02-01 00:00:00pages
207-214issue
2eissn
0818-9641issn
1440-1711pii
icb201689journal_volume
95pub_type
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journal_title:Immunology and cell biology
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