ArticleProceedings of the National Academy of Sciences of the United States of America2016
Impaired NK-mediated regulation of T-cell activity in multiple sclerosis is reconstituted by IL-2 receptor modulation.
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 114 papers, 1 of them a synthesis that pooled it.
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Who cites it
114 citing papers in PubMed, 1 synthesis or guideline pooled it, 178 citations in OpenAlex.
- Regulatory T Cell- and Natural Killer Cell-Mediated Inflammation, Cerebral Vasospasm, and Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage-A Systematic Review and Meta-Analysis Approach.International journal of molecular sciences · 2025Pooled it
- A CD8Nature communications · 2021Trial
- Adaptive Features of Natural Killer Cells in Multiple Sclerosis.Frontiers in immunology · 2019Trial
- Natural Killer Cells Regulate Th17 Cells After Autologous Hematopoietic Stem Cell Transplantation for Relapsing Remitting Multiple Sclerosis.Frontiers in immunology · 2018Trial
- Harnessing Natural Killer Cells: From Neuroimmunology to Novel Therapies for Central Nervous System Diseases.MedComm · 2026Review
- Mesenchymal stromal cells and neuroinflammation: a multimodal approach to neuroprotection and future therapeutic horizons.Translational neurodegeneration · 2026Review
- IL-15 in alopecia areata: the immune tolerance mechanistic insights and translational perspectives.Frontiers in medicine · 2026Review
- Innate Immunity in the Pathogenesis of Selected Autoimmune Neurological Diseases.Journal of clinical medicine · 2025Review
- CXCR3-mediated natural killer cell infiltration exacerbates white matter injury after intracerebral haemorrhage.Brain : a journal of neurology · 2025Article
- Peripheral HLA-DRNeurology(R) neuroimmunology & neuroinflammation · 2025Article
- Butyrate enhances CD56Genes and immunity · 2025Article
- Neuroinflammation causes mitral cell dysfunction and olfactory impairment in a multiple sclerosis model.Journal of neuroinflammation · 2025Article
- Treatment of Alzheimer's Disease subjects with expanded non-genetically modified autologous natural killer cells (SNK01): a phase I study.Alzheimer's research & therapy · 2025Article
- The Polygenic Nature of Multiple Sclerosis: Genetic Variants, Immunological Modulation, and Environmental Connections.Endocrine, metabolic & immune disorders drug targets · 2025Review
- Natural killer cells in multiple sclerosis: foe or friends?Frontiers in cellular neuroscience · 2025Review
- Comprehensive snapshots of natural killer cells functions, signaling, molecular mechanisms and clinical utilization.Signal transduction and targeted therapy · 2024Review
- Longitudinal analysis of peripheral immune cells in patients with multiple sclerosis treated with anti-CD20 therapy.Annals of clinical and translational neurology · 2024Article
- The ratio of circulating CD56Heliyon · 2024Article
- CNS Resident Innate Immune Cells: Guardians of CNS Homeostasis.International journal of molecular sciences · 2024Review
- Altered CD226/TIGIT expressions were associated with NK phenotypes in primary antiphospholipid syndrome and affected by IL-4/JAK pathway.Clinical and experimental immunology · 2024Article
54 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS) resulting from a breakdown in peripheral immune tolerance. Although a beneficial role of natural killer (NK)-cell immune-regulatory function has been proposed, it still needs to be elucidated whether NK cells are functionally impaired as part of the disease. We observed NK cells in active MS lesions in close proximity to T cells. In accordance with a higher migratory capacity across the blood-brain barrier, CD56(bright) NK cells represent the major intrathecal NK-cell subset in both MS patients and healthy individuals. Investigating the peripheral blood and cerebrospinal fluid of MS patients treated with natalizumab revealed that transmigration of this subset depends on the α4β1 integrin very late antigen (VLA)-4. Although no MS-related changes in the migratory capacity of NK cells were observed, NK cells derived from patients with MS exhibit a reduced cytolytic activity in response to antigen-activated CD4(+) T cells. Defective NK-mediated immune regulation in MS is mainly attributable to a CD4(+) T-cell evasion caused by an impaired DNAX accessory molecule (DNAM)-1/CD155 interaction. Both the expression of the activating NK-cell receptor DNAM-1, a genetic alteration consistently found in MS-association studies, and up-regulation of the receptor's ligand CD155 on CD4(+) T cells are reduced in MS. Therapeutic immune modulation of IL-2 receptor restores impaired immune regulation in MS by increasing the proportion of CD155-expressing CD4(+) T cells and the cytolytic activity of NK cells.
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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.