Microglial TNF-α-Dependent Elevation of MHC Class I Expression on Brain Endothelium Induced by Amyloid-Beta Promotes T Cell Transendothelial Migration
Abstract
The blood-brain barrier (BBB) normally bars peripheral T lymphocytes from entering the cerebrum. Interestingly, activated T cells exist as infiltrates in the brains of Alzheimer's disease (AD) patients, but little is known about the mechanisms involved. In this study, we observed significantly higher MHC class I expression in rat brain endothelial cells compared with controls following the induction of experimental AD models. An in vitro BBB model, which was constructed with human brain microvascular endothelial cells, was established to study the mechanisms underlying the transendothelial migration of T cells. Using in vitro studies, we demonstrated that secretion of TNF-α from Aβ1-42-treated BV2 microglia contributes to the elevated expression of MHC class I on the brain microvessel endothelium. Transmigration assays and adhesion assays confirmed that the upregulation of MHC class I molecules was associated with T cell transendothelial migration. MHC class I knock-down in HBMECs significantly attenuated the migratory and adhesive capability of the T cells. Interestingly, a TNF-α neutralizing antibody effectively blocked the transendothelial migration of T cells triggered by treatment with the supernatant from Aβ1-42-treated BV2 microglia. We propose that microglia-derived TNF-α upregulates MHC class I molecule expression on brain endothelial cells, which represents a mechanism of T cell migration into the brain. This study may provide a new insight into the potential pathomechanism of Alzheimer's disease.
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T cell migration into the brain through the BBB in AD depends on TNF-α expressed by microglia, which induce expression of MHC class I on brain endothelial cells.
“In this study it was shown that T cell migration into the brain through the BBB in AD depends on the TNF-α expressed by microglia, which induce the expression of MHC class I (MHC-I) on brain ECs (Yang et al., 2013).”
From The impact of microglial activation on blood-brain barrier in brain diseases (2014) · cites this paper as Yang et al., 2013
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- Authors
- Yang, Y.-M., Shang, D.-S., Zhao, W.-D., Fang, W.-G., & Chen, Y.-H.
- Affiliations
- China Medical University (CN)
- Venue
- Neurochemical Research
- Published
- 2013-08-29
- Volume
- 38
- Issue
- 11
- Pages
- 2295-2304
- ISSN
- 0364-3190 (ISSN-L)
- 1573-6903
- OpenAlex
- W2074850583
- Cited by
- 57
- References
- 65
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 5 · 2022: 4 · 2021: 7 · 2020: 4 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 4 · 2015: 12 · 2014: 4 · 2013: 1
- FWCI
- 3.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neurochemical Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Alzheimer's disease, amyloid-beta, microglia, TNF-α, MHC class I, brain endothelium, blood-brain barrier, T cell infiltration, brain microvascular endothelial cells, BV-2 cells, T cell adhesion
- MeSH terms
- Alzheimer Disease, Animals, Blood-Brain Barrier, Cell Movement, Cells, Cultured, Endothelium, Vascular, Humans, Male, Peptide Fragments, T-Lymphocytes, Tumor Necrosis Factor-alpha, Histocompatibility Antigens Class I, Up-Regulation, Amyloid beta-Peptides, Rats, Wistar, Microglia, Rats, Transendothelial and Transepithelial Migration
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