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Astrocytes have the capacity to act as antigen-presenting cells in the Parkinson’s disease brain
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Astrocytes have the capacity to act as antigen-presenting cells in the Parkinson’s disease brain
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Journal Article
Astrocytes have the capacity to act as antigen-presenting cells in the Parkinson’s disease brain
2020
Overview
Background
Many lines of evidence suggest that accumulation of aggregated alpha-synuclein (αSYN) in the Parkinson’s disease (PD) brain causes infiltration of T cells. However, in which ways the stationary brain cells interact with the T cells remain elusive. Here, we identify astrocytes as potential antigen-presenting cells capable of activating T cells in the PD brain. Astrocytes are a major component of the nervous system, and accumulating data indicate that astrocytes can play a central role during PD progression.
Methods
To investigate the role of astrocytes in antigen presentation and T-cell activation in the PD brain, we analyzed
post mortem
brain tissue from PD patients and controls. Moreover, we studied the capacity of cultured human astrocytes and adult human microglia to act as professional antigen-presenting cells following exposure to preformed αSYN fibrils.
Results
Our analysis of post mortem brain tissue demonstrated that PD patients express high levels of MHC-II, which correlated with the load of pathological, phosphorylated αSYN. Interestingly, a very high proportion of the MHC-II co-localized with astrocytic markers. Importantly, we found both perivascular and infiltrated CD4
+
T cells to be surrounded by MHC-II expressing astrocytes, confirming an astrocyte T cell cross-talk in the PD brain. Moreover, we showed that αSYN accumulation in cultured human astrocytes triggered surface expression of co-stimulatory molecules critical for T-cell activation, while cultured human microglia displayed very poor antigen presentation capacity. Notably, intercellular transfer of αSYN/MHC-II deposits occurred between astrocytes via tunneling nanotubes, indicating spreading of inflammation in addition to toxic protein aggregates.
Conclusions
In conclusion, our data from histology and cell culture studies suggest an important role for astrocytes in antigen presentation and T-cell activation in the PD brain, highlighting astrocytes as a promising therapeutic target in the context of chronic inflammation.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
/ Antigen-Presenting Cells - immunology
/ Antigen-Presenting Cells - metabolism
/ Antigen-Presenting Cells - pathology
/ Antigens
/ Biomedical and Life Sciences
/ Ethanol
/ Female
/ Fibrils
/ Humans
/ Major histocompatibility complex
/ Male
/ MHC-II
/ Parkinson Disease - immunology
/ Parkinson Disease - metabolism
/ Parkinson Disease - pathology
/ Peptides
