ArticleJournal of immunology (Baltimore, Md. : 1950)2011
Unexpected role for granzyme K in CD56bright NK cell-mediated immunoregulation of multiple sclerosis.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
94 citing papers in PubMed, 1 synthesis or guideline pooled it, 151 citations in OpenAlex.
- Immunopathology of and potential therapeutics for secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome: a translational perspective.Experimental & molecular medicine · 2024Pooled it
- Blood biomarker dynamics in people with relapsing multiple sclerosis treated with cladribine tablets: results of the 2-year MAGNIFY-MS study.Frontiers in immunology · 2025Trial
- Unconventional functions of natural killer cells in homeostasis and disease.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- Natural Killer Cells: Dual Regulators and Therapeutic Targets in Multiple Sclerosis Immunopathogenesis.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Review
- Mesenchymal stromal cells and neuroinflammation: a multimodal approach to neuroprotection and future therapeutic horizons.Translational neurodegeneration · 2026Review
- Is the Association of Granzyme B and the Exported Parasite Hsp70 a Possible Trojan Horse of Severe Malaria?Advances in experimental medicine and biology · 2026Article
- Redefining multiple sclerosis therapy through microbial immunomodulation and epigenetic control.Journal of translational autoimmunity · 2025Review
- Innate Immunity in the Pathogenesis of Selected Autoimmune Neurological Diseases.Journal of clinical medicine · 2025Review
- TCF19 drives a broad transcriptional program that potentiates optimal innate and adaptive functions of antiviral NK cells.Nature immunology · 2025Article
- GZMK Facilitates Experimental Rheumatoid Arthritis Progression by Interacting with CCL5 and Activating the ERK Signaling.Inflammation · 2025Article
- NKG7 is a Stable Marker of Cytotoxicity Across Immune Contexts and Within the Tumor Microenvironment.European journal of immunology · 2025Article
- Natural killer cells in multiple sclerosis: foe or friends?Frontiers in cellular neuroscience · 2025Review
- Lymphocyte signatures correspond to clinical phenotypes in autoimmune limbic encephalitis.Brain communications · 2025Article
- High-dimensional single-cell analysis of human natural killer cell heterogeneity.Nature immunology · 2024Article
- The role of CD56Journal of neuroinflammation · 2024Review
- Ozanimod-mediated remission in experimental autoimmune encephalomyelitis is associated with enhanced activity of CNS CD27Frontiers in immunology · 2024Article
- Natural killer cells in the central nervous system.Cell communication and signaling : CCS · 2023Review
- Single cell transcriptomics shows that malaria promotes unique regulatory responses across multiple immune cell subsets.Nature communications · 2023Article
- How Does Vitamin D Affect Immune Cells Crosstalk in Autoimmune Diseases?International journal of molecular sciences · 2023Review
- Role of the granzyme family in rheumatoid arthritis: Current Insights and future perspectives.Frontiers in immunology · 2023Review
34 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
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Functional NK cell deficiencies are associated with autoimmune diseases, including multiple sclerosis. NK cells can promote or inhibit adaptive immunity via either cytokine production or cytotoxicity toward immature dendritic cells and activated T cells. In humans, this immunoregulatory role resides in the CD56(bright) NK cell subset, which is selectively expanded by daclizumab, a CD25-blocking Ab that suppresses multiple sclerosis-associated inflammation. The objective of this study was to investigate the molecular mechanisms underlying the cytotoxicity of NK cells toward activated T cells. We demonstrated that NK cells induce caspase-independent apoptosis that requires NK cell degranulation and causes mitochondrial dysfunction in activated T cells. Although both granzyme A and granzyme K (GrK) can mediate this form of apoptosis, quantitatively we observed preferential transfer of GrK to target cells. Consequently, gene silencing of GrK in the NK-92 cell line, which retains functional characteristics of CD56(bright) NK cells, profoundly inhibited the ability of NK-92 cells to kill activated syngeneic T cells. Finally, we demonstrated that daclizumab treatment significantly enhanced this newly defined mechanism of cytotoxicity by CD56(bright) NK cells. Our study describes the important physiological role that GrK plays in immunoregulation of adaptive immunity in humans and indicates that therapeutic exploitation of this pathway is beneficial in controlling autoimmunity.
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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.