ArticleProceedings of the National Academy of Sciences of the United States of America2013
CNS-specific immunity at the choroid plexus shifts toward destructive Th2 inflammation in brain aging.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 179 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
179 citing papers in PubMed, 282 citations in OpenAlex.
- Intranasal insulin modulates cerebrospinal fluid markers of neuroinflammation in mild cognitive impairment and Alzheimer's disease: a randomized trial.Scientific reports · 2022 · on this mapTrial
- Nutritional regulation of gut-brain immune crosstalk across the lifespan.Gut microbes · 2026Review
- Cytokine circuits in CNS homeostasis and disease.Nature immunology · 2026Review
- Chemokine levels in the murine brain from early postnatal development to aging.Brain, behavior, & immunity - health · 2026Article
- Review
- Aged circulating CD8Immunity · 2026Article
- Gut Microbiota and Autoimmune Diseases: The Therapeutic Potential of Probiotics.Current microbiology · 2026Review
- Central Nervous System T-cell immune architecture, and not HIV burden, tracks with cognition under long-term viral suppression.PLoS pathogens · 2026Article
- Living rent free in your head: resident memory T cells.ImmunoHorizons · 2026Review
- Opioid-induced transcriptional reprogramming of cerebrospinal fluid immune cells is associated with neuroinflammatory signaling in antiretroviral treated SIV-infected rhesus macaques.Journal of neuroinflammation · 2026Article
- Article
- Choroid plexus enlargement contributes to CSVD progression and white matter microstructural deterioration via brain-fluid dysregulation.Alzheimer's research & therapy · 2026Article
- Opioid-induced transcriptional reprogramming of cerebrospinal fluid immune cells drives neuroinflammation in SIV-infected rhesus macaques.Research square · 2026Article
- Treg-microglia crosstalk in Alzheimer's disease: stage-dependent dynamics, molecular mechanisms, and translational challenge.Frontiers in aging neuroscience · 2026Review
- Revitalizing T cells: breakthroughs and challenges in overcoming T cell exhaustion.Signal transduction and targeted therapy · 2026Review
- Meningeal lymphatics as a therapeutic target for neurodegenerative disorders.Translational neurodegeneration · 2025Review
- The aging choroid plexus and its relationship with gut dysbiosis and Klotho decline: possible intervention strategies.GeroScience · 2025Review
- Microglia-Mediated Neuroinflammation Through Phosphatidylinositol 3-Kinase Signaling Causes Cognitive Dysfunction.International journal of molecular sciences · 2025Review
- Age-related Vascular Alterations in the Choroid Plexus: Novel Insights from Pathophysiology and Imaging Studies.Aging and disease · 2025Review
- Article
119 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
The adaptive arm of the immune system has been suggested as an important factor in brain function. However, given the fact that interactions of neurons or glial cells with T lymphocytes rarely occur within the healthy CNS parenchyma, the underlying mechanism is still a mystery. Here we found that at the interface between the brain and blood circulation, the epithelial layers of the choroid plexus (CP) are constitutively populated with CD4(+) effector memory cells with a T-cell receptor repertoire specific to CNS antigens. With age, whereas CNS specificity in this compartment was largely maintained, the cytokine balance shifted in favor of the T helper type 2 (Th2) response; the Th2-derived cytokine IL-4 was elevated in the CP of old mice, relative to IFN-γ, which decreased. We found this local cytokine shift to critically affect the CP epithelium, triggering it to produce the chemokine CCL11 shown to be associated with cognitive dysfunction. Partial restoration of cognitive ability in aged mice, by lymphopenia-induced homeostasis-driven proliferation of memory T cells, was correlated with restoration of the IL-4:IFN-γ ratio at the CP and modulated the expression of plasticity-related genes at the hippocampus. Our data indicate that the cytokine milieu at the CP epithelium is affected by peripheral immunosenescence, with detrimental consequences to the aged brain. Amenable to immunomodulation, this interface is a unique target for arresting age-related cognitive decline.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.