IFN-γ-induced increase in the mobility of MHC class II compartments in astrocytes depends on intermediate filaments
Open accessAbstract
Background: In immune-mediated diseases of the central nervous system, astrocytes exposed to interferon-γ (IFN-γ) can express major histocompatibility complex (MHC) class II molecules and antigens on their surface. MHC class II molecules are thought to be delivered to the cell surface by membrane-bound vesicles. However, the characteristics and dynamics of this vesicular traffic are unclear, particularly in reactive astrocytes, which overexpress intermediate filament (IF) proteins that may affect trafficking. The aim of this study was to determine the mobility of MHC class II vesicles in wild-type (WT) astrocytes and in astrocytes devoid of IFs. Methods: The identity of MHC class II compartments in WT and IF-deficient astrocytes 48 h after IFN-γ activation was determined immunocytochemically by using confocal microscopy. Time-lapse confocal imaging and Alexa Fluor 546-dextran labeling of late endosomes/lysosomes in IFN-γ treated cells was used to characterize the motion of MHC class II vesicles. The mobility of vesicles was analyzed using ParticleTR software. Results: Confocal imaging of primary cultures of WT and IF-deficient astrocytes revealed IFN-γ induced MHC class II expression in late endosomes/lysosomes, which were specifically labeled with Alexa Fluor 546-conjugated dextran. Live imaging revealed faster movement of dextran-positive vesicles in IFN-γ-treated than in untreated astrocytes. Vesicle mobility was lower in IFN-γ-treated IF-deficient astrocytes than in WT astrocytes. Thus, the IFN-γ-induced increase in the mobility of MHC class II compartments is IF-dependent. Conclusions: Since reactivity of astrocytes is a hallmark of many CNS pathologies, it is likely that the up-regulation of IFs under such conditions allows a faster and therefore a more efficient delivery of MHC class II molecules to the cell surface. In vivo, such regulatory mechanisms may enable antigen-presenting reactive astrocytes to respond rapidly and in a controlled manner to CNS inflammation.
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Astrocyte endfeet line the abluminal aspect of endothelial cells and are important for the formation and maintenance of the blood-brain-barrier.
“Astrocyte endfeet line the abluminal aspect of endothelial cells and are important for the formation and maintenance of the blood-brain-barrier (29).”
From Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice (2013) · cites this paper as [29]
The Background and Conclusions discuss astrocyte antigen presentation and MHC class II trafficking, not astrocyte endfeet or the blood–brain barrier. Searches for endfeet, endothelial cells, and blood–brain barrier formation and maintenance found no passage addressing the claim in our copy. (LLM, conf=0.75)
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- Authors
- Vardjan, N., Gabrijel, M., Potokar, M., Švajger, U., Kreft, M., Jeras, M., de Pablo, Y., Faiz, M., Pekny, M., & Zorec, R.
- Affiliations
- University of Ljubljana (SI)
- Blood Transfusion Centre of Slovenia (SI)
- University of Gothenburg (SE)
- Corresponding author
- Zorec, Robert
- ORCID
- Venue
- Journal of Neuroinflammation
- Published
- 2012-06-26
- Volume
- 9
- Issue
- 1
- Pages
- 144-144
- ISSN
- 1742-2094 (ISSN-L)
- PMC
- PMC3423045
- OpenAlex
- W2139576028
- Cited by
- 117
- References
- 54
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 4 · 2023: 7 · 2022: 5 · 2021: 7 · 2020: 9 · 2019: 13 · 2018: 8 · 2017: 14 · 2016: 10 · 2015: 14 · 2014: 8 · 2013: 4 · 2012: 2
- FWCI
- 4.24
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Neuroinflammation (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- European Commission (279017, 237956)
- Javna Agencija za Raziskovalno Dejavnost RS (J3-0133, P3-310, L1-2402, J3-4146, J3-0031)
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Keywords
- interferon-gamma, MHC class II, astrocytes, intermediate filaments, vesicle mobility, late endosomes, lysosomes, antigen presentation, reactive astrocytes, vesicle trafficking, neuroinflammation
- MeSH terms
- Animals, Histocompatibility Antigens Class II, Astrocytes, Cell Compartmentation, Cells, Cultured, Interferon-gamma, Intermediate Filament Proteins, Mice, Inbred C57BL, Up-Regulation, Mice, Knockout, Protein Transport, Mice, Mice, 129 Strain
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