Peripheral T cells derived from Alzheimer's disease patients overexpress CXCR2 contributing to its transendothelial migration, which is microglial TNF-α-dependent
Abstract
The mechanism of circulating T cells entry into the brain in Alzheimer's diseases (AD) remains unclear. Here, we showed that peripheral T cells derived from AD patients overexpress CXCR2 to enhance its transendothelial migration. T cells migration through in vitro blood-brain barrier model was effectively blocked by anti-CXCR2 antibody or IL-8 (a CXCR2 ligand) RNAi in human brain microvascular endothelial cells (HBMECs). Amyloid beta (Abeta) injection in rat hippocampus upregulated CXCR2 expression accompanied with increased T cells occurrence in the brain, and this enhanced T cells entry was effectively blocked by CXCR2 antagonist. Furthermore, anti-TNF-alpha antibody blocked IL-8 production in HBMECs and T cells transendothelial migration caused by the culture supernatant of microglia treated with Abeta. Blockage of intracerebral TNF-alpha abolished the upregulation of CXCR2 in peripheral T cells and the increased T cells occurrence in the brain induced by Abeta injection in rat hippocampus. These data suggest that CXCR2 overexpression in peripheral T cells is intracerebral microglial TNF-alpha-dependent and TNF-alpha primes T cells transendothelial migration in Alzheimer's diseases.
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CXCR2 is intracerebral microglial TNF-α-dependent.
“Furthermore, recent evidence revealed that peripheral T cells of AD patients overexpressed CXCR2 (CXC chemokine receptor 2), which is intracerebral microglial TNF-α-dependent and is associated with T-cell adhesion on brain endothelia and transendothelial migration [167].”
From PKR, the double stranded RNA‐dependent protein kinase as a critical target in Alzheimer's disease (2009) · cites this paper as [167]
Peripheral T cells of Alzheimer's disease patients overexpress CXCR2.
“Furthermore, recent evidence revealed that peripheral T cells of AD patients overexpressed CXCR2 (CXC chemokine receptor 2), which is intracerebral microglial TNF-α-dependent and is associated with T-cell adhesion on brain endothelia and transendothelial migration [167].”
From PKR, the double stranded RNA‐dependent protein kinase as a critical target in Alzheimer's disease (2009) · cites this paper as [167]
CXCR2 is associated with T-cell adhesion on brain endothelia and transendothelial migration.
“Furthermore, recent evidence revealed that peripheral T cells of AD patients overexpressed CXCR2 (CXC chemokine receptor 2), which is intracerebral microglial TNF-α-dependent and is associated with T-cell adhesion on brain endothelia and transendothelial migration [167].”
From PKR, the double stranded RNA‐dependent protein kinase as a critical target in Alzheimer's disease (2009) · cites this paper as [167]
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The blood-brain barrier in Alzheimer’s disease
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- Authors
- Liu, Y.-J., Guo, D.-W., Tian, L., Shang, D.-S., Zhao, W.-D., Li, B., Fang, W.-G., Zhu, L., & Chen, Y.-H.
- Affiliations
- China Medical University (CN)
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2010-02
- Volume
- 31
- Issue
- 2
- Pages
- 175-188
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2017923860
- Cited by
- 92
- References
- 5
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 6 · 2022: 6 · 2021: 9 · 2020: 4 · 2019: 6 · 2018: 6 · 2017: 5 · 2016: 3 · 2015: 8 · 2014: 7 · 2013: 9 · 2012: 5
- FWCI
- 1.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Johns Hopkins University
- China Medical University
- National Institute of Neurological Disorders and Stroke
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Alzheimer's disease, peripheral T cells, CXCR2, transendothelial migration, blood-brain barrier, microglia, TNF-α, interleukin-8, amyloid-beta, brain microvascular endothelial cells
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Animals, Autoantibodies, Blood-Brain Barrier, Brain, Cell Movement, Endothelium, Vascular, Female, Humans, Male, T-Lymphocytes, Tumor Necrosis Factor-alpha, Interleukin-8, Amyloid beta-Peptides, Rats, Wistar, Microglia, Receptors, Interleukin-8B, Rats, Microvessels
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