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Astrocytes with Alz...
Astrocytes with Alzheimer’s disease pathology provoke lipid droplet mediated cell-to-cell propagation of MHC II complexes
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- Beretta, Chiara (author)
- Uppsala universitet,Molekylär geriatrik
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- Dakhel, Abdulkhalek (author)
- Uppsala universitet,Molekylär geriatrik
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- Eltom, Khalid (author)
- Molekylär geriatrik, Molecular Geriatrics, Uppsala University
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- Rosqvist, Fredrik, 1985- (author)
- Uppsala universitet,Klinisk nutrition och metabolism,Institutionen för medicinska vetenskaper
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- Uzoni, Simon (author)
- Department of Chemistry and Molecular Biology, University of Gothenburg
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- Mothes, Tobias (author)
- Uppsala universitet,Institutionen för folkhälso- och vårdvetenskap
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- Rostami, Jinar (author)
- Molekylär geriatrik, Molecular Geriatrics, Uppsala University
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- Fletcher, John S. (author)
- Department of Chemistry and Molecular Biology, University of Gothenburg
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- Risérus, Ulf, 1967- (author)
- Uppsala universitet,Klinisk nutrition och metabolism,Institutionen för medicinska vetenskaper
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- Sehlin, Dag, 1976- (author)
- Uppsala universitet,Molekylär geriatrik
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- Michno, Wojciech (author)
- Uppsala universitet,Molekylär geriatrik,Science for Life Laboratory, SciLifeLab
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- Erlandsson, Anna (author)
- Uppsala universitet,Molekylär geriatrik
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(creator_code:org_t)
- English.
- Related links:
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https://urn.kb.se/re...
Abstract
Subject headings
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- Background. Astrocytes are critical for maintaining brain homeostasis, but are also highly involved in neuroinflammation. In the Alzheimer disease (AD) brain, reactive, inflammatory astrocytes are situated closely around amyloid β (Aβ) plaques. We have previously shown that reactive astrocytes ingest large quantities of soluble Aβ aggregates, but are unable to degrade the material, which leads to intracellular Aβ accumulation and severe cellular stress. A common response to cellular stress is the formation of lipid droplets (LDs). Novel data indicate that LDs play an important role in inflammatory processes. However, the involvement of LDs in AD inflammation and progression remains unclear.Methods. The aim of this study was to investigate how astrocytic Aβ pathology affects lipid metabolism and antigen presentation. For this purpose, human induced pluripotent stem cell (iPSC) derived astrocytes were exposed to soluble Aβ42 aggregates and analyzed over time, using a battery of experimental approaches.Results. Our results show that Aβ exposure induces LD accumulation in astrocytes, although the overall lipid composition remains unchanged. Moreover, astrocytes transfer LDs to neighboring cells via tunneling nanotubes (TNTs) and extracellular vesicle (EVs). Interestingly, we found that the antigen presenting protein major histocompatibility complex II (MHCII) is present inside LDs, suggesting an active role of LDs in astrocytic antigen presentation. Immunohistochemical analysis of human brain tissue verified the presence of LD-loaded MHCII+ astrocytes in AD individuals. Moreover, we found infiltrated CD4+ T cells to be in close contact with astrocytes, confirming an astrocyte T cell cross-talk in the AD brainConclusions. Taken together, our data show that Aβ pathology drastically affects lipid storage in astrocytes, which in turn modulates the astrocytic antigen presentation, indicating a role for astrocytic LDs in T cell responses in the AD brain.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Alzheimer’s disease
- Aβ
- astrocytes
- lipid droplets
- inflammation
- MHCII
- T cells
- Molekylär medicin
- Molecular Medicine
Publication and Content Type
- vet (subject category)
- ovr (subject category)
To the university's database
- By the author/editor
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Beretta, Chiara
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Dakhel, Abdulkha ...
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Eltom, Khalid
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Rosqvist, Fredri ...
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Uzoni, Simon
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Mothes, Tobias
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show more...
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Rostami, Jinar
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Fletcher, John S ...
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Risérus, Ulf, 19 ...
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Sehlin, Dag, 197 ...
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Michno, Wojciech
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Erlandsson, Anna
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- By the university
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Uppsala University