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IFN-γ-dependent activation of the brain’s choroid plexus for CNS immune surveillance and repair
Abstract
Infiltrating T cells and monocyte-derived macrophages support central nervous system repair. Although infiltration of leucocytes to the injured central nervous system has recently been shown to be orchestrated by the brain's choroid plexus, the immunological mechanism that maintains this barrier and regulates its activity as a selective gate is poorly understood. Here, we hypothesized that CD4(+) effector memory T cells, recently shown to reside at the choroid plexus stroma, regulate leucocyte trafficking through this portal through their interactions with the choroid plexus epithelium. We found that the naïve choroid plexus is populated by T helper 1, T helper 2 and regulatory T cells, but not by encephalitogenic T cells. In vitro findings revealed that the expression of immune cell trafficking determinants by the choroid plexus epithelium is specifically induced by interferon-γ. Tumour necrosis factor-α and interferon-γ reciprocally controlled the expression of their receptors by the choroid plexus epithelium, and had a synergistic effect in inducing the epithelial expression of trafficking molecules. In vivo, interferon-γ-dependent signalling controlled trafficking through the choroid plexus; interferon-γ receptor knockout mice exhibited reduced levels of T cells and monocyte entry to the cerebrospinal fluid and impaired recovery following spinal cord injury. Moreover, reduced expression of trafficking molecules by the choroid plexus was correlated with reduced CD4(+) T cells in the choroid plexus and cerebrospinal fluid of interferon-γ receptor knockout mice. Similar effect on the expression of trafficking molecules by the choroid plexus was found in bone-marrow chimeric mice lacking interferon-γ receptor in the central nervous system, or reciprocally, lacking interferon-γ in the circulation. Collectively, our findings attribute a novel immunological plasticity to the choroid plexus epithelium, allowing it to serve, through interferon-γ signalling, as a tightly regulated entry gate into the central nervous system for circulating leucocytes immune surveillance under physiological conditions, and for repair following acute injury.
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“In spinal cord injury mouse model, knockout of IFN-γ receptor reduced the infiltration of T cells and monocytes to the CSF, impaired the resolution of inflammation and attenuated recovery.”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [147]
In the citing paper
“IFN-γ was verified as the crucial player in the expression of resolving macrophages attracting factors by the choroid plexus epithelium.”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [147]
In the citing paper
“Immunostaining of the in vitro cell culture and the choroid plexus from mice revealed that TNF-α and IFN-γ reciprocally control the expression of their receptors in the choroid plexus, through which way they synergistically activate the choroid plexus epithelium to express trafficking molecules.”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [147]
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Role of neuroinflammation in neurodegeneration development
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Self-citation
Metadata
- Authors
- Kunis, G., Baruch, K., Rosenzweig, N., Kertser, A., Miller, O., Berkutzki, T., & Schwartz, M.
- Affiliations
- Weizmann Institute of Science (IL)
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-10-01
- Volume
- 136
- Issue
- 11
- Pages
- 3427-3440
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2112350141
- Cited by
- 321
- References
- 57
- Citations by year
- 2026: 14 · 2025: 28 · 2024: 27 · 2023: 31 · 2022: 34 · 2021: 26 · 2020: 28 · 2019: 23 · 2018: 18 · 2017: 25 · 2016: 22 · 2015: 25 · 2014: 17 · 2013: 3
- FWCI
- 12.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
- Keywords
- choroid plexus, interferon-gamma, choroid plexus epithelium, Th1 cells, regulatory T cells, Th2 cells, interferon-gamma receptor, TNF-α, cerebrospinal fluid, spinal cord injury, CNS repair, immune surveillance, monocyte-derived macrophages, CD4+ T cells, bone marrow chimeric mice
- MeSH terms
- Interferon gamma Receptor, Animals, Cell Movement, Central Nervous System, Choroid Plexus, Epithelium, Female, Interferon-gamma, Male, Mice, Inbred C57BL, Receptors, Interferon, Mice, Knockout, Protein Transport, Mice
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