ArticleProceedings of the National Academy of Sciences of the United States of America2016
CD8 T cell-mediated killing of orexinergic neurons induces a narcolepsy-like phenotype in mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
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
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 141 citations in OpenAlex.
- Narcolepsy and psychosis: A systematic review.Acta psychiatrica Scandinavica · 2021Pooled it
- Immunocyte phenotypes underlying the causal autoimmune features in narcolepsy type 1.Journal of thoracic disease · 2026Article
- Therapeutic potential of targeting the orexin (hypocretin) system in sleep disorders.Nature reviews. Endocrinology · 2026Review
- Increased Numbers of CD4Annals of neurology · 2026Article
- Cytokines in narcolepsy type 1: pathogenic relevance, biomarker potential, and future directions.Frontiers in neurology · 2026Review
- A Comprehensive Review of Current and Emerging Treatments for Narcolepsy Type 1.Journal of clinical medicine · 2025Review
- Animal Models of Narcolepsy: From Orexin Deficiency to Immune Mechanisms and Regenerative Therapies.Current issues in molecular biology · 2025Review
- Association between cytokines and neuropsychiatric symptoms in paediatric narcolepsy patients: a cross-sectional study.BMC neurology · 2025Article
- The interaction between orexin, sleep deprivation and Alzheimer's disease: Unveiling an Emerging Connection.The journal of physiological sciences : JPS · 2025Review
- Repetitive antigen stimulation in the periphery dictates the composition and recall responses of brain-resident memory CD8Cell reports · 2025Article
- The neuroimmune connectome in health and disease.Nature · 2025Review
- Increased neutrophil-to-lymphocyte ratio as a possible marker to detect neuroinflammation in patients with narcolepsy type 1.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2025Article
- The Role of T Cells in the Pathogenesis of Narcolepsy Type 1: A Narrative Review.International journal of molecular sciences · 2024Review
- Associations between T-cell traits and narcolepsy type 1: new insights from a Mendelian randomization study.Frontiers in neurology · 2024Article
- The immunopathogenesis of narcolepsy type 1.Nature reviews. Immunology · 2024Review
- Article
- CD8+ T cells recognizing a neuron-restricted antigen injure axons in a model of multiple sclerosis.The Journal of clinical investigation · 2023Article
- Conserved and cell type-specific transcriptional responses to IFN-γ in the ventral midbrain.Brain, behavior, and immunity · 2023Article
- Narcolepsy type I-associated DNA methylation and gene expression changes in the human leukocyte antigen region.Scientific reports · 2023Article
- Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy.Nature communications · 2023Article
4 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
14 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Narcolepsy with cataplexy is a rare and severe sleep disorder caused by the destruction of orexinergic neurons in the lateral hypothalamus. The genetic and environmental factors associated with narcolepsy, together with serologic data, collectively point to an autoimmune origin. The current animal models of narcolepsy, based on either disruption of the orexinergic neurotransmission or neurons, do not allow study of the potential autoimmune etiology. Here, we sought to generate a mouse model that allows deciphering of the immune mechanisms leading to orexin(+) neuron loss and narcolepsy development. We generated mice expressing the hemagglutinin (HA) as a "neo-self-antigen" specifically in hypothalamic orexin(+) neurons (called Orex-HA), which were transferred with effector neo-self-antigen-specific T cells to assess whether an autoimmune process could be at play in narcolepsy. Given the tight association of narcolepsy with the human leukocyte antigen (HLA) HLA-DQB1*06:02 allele, we first tested the pathogenic contribution of CD4 Th1 cells. Although these T cells readily infiltrated the hypothalamus and triggered local inflammation, they did not elicit the loss of orexin(+) neurons or clinical manifestations of narcolepsy. In contrast, the transfer of cytotoxic CD8 T cells (CTLs) led to both T-cell infiltration and specific destruction of orexin(+) neurons. This phenotype was further aggravated upon repeated injections of CTLs. In situ, CTLs interacted directly with MHC class I-expressing orexin(+) neurons, resulting in cytolytic granule polarization toward neurons. Finally, drastic neuronal loss caused manifestations mimicking human narcolepsy, such as cataplexy and sleep attacks. This work demonstrates the potential role of CTLs as final effectors of the immunopathological process in narcolepsy.
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.