ArticleThe Journal of allergy and clinical immunology2013
Defective actin accumulation impairs human natural killer cell function in patients with dedicator of cytokinesis 8 deficiency.
Article in The Journal of allergy and clinical immunology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.
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Who cites it
82 citing papers in PubMed, 1 synthesis or guideline pooled it, 130 citations in OpenAlex.
- Monogenic etiologies of persistent human papillomavirus infections: A comprehensive systematic review.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Pooled it
- Pediatric DOCK8 Deficiency Beyond Infections and Atopy: An Immunoactinopathy with Immune Dysregulation and Multisystem Involvement.Children (Basel, Switzerland) · 2026Article
- Targeting IL27RA Enhances Immunotherapy in Triple-Negative Breast Cancer by Modulating Tumor Cells and the Tumor Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Immune-related actinopathies at the cross-road of immunodeficiency, autoimmunity and autoinflammation.Nature reviews. Immunology · 2026Review
- DOCK8 in immune cells: roles and mechanisms.Frontiers in immunology · 2026Review
- Analysis of genes involved in immune response in children with HLH - case series.Pediatric rheumatology online journal · 2025Article
- Hemophagocytic Lymphohistiocytosis Gene Variants in Severe COVID-19 Cytokine Storm Syndrome.Viruses · 2025Article
- Clinical, immunologic, and genetic characteristics of 148 patients with natural killer cell deficiency.The Journal of allergy and clinical immunology · 2025Article
- Reconstitution of Norovirus-Specific T-Cell Responses Following Hematopoietic Stem Cell Transplantation in Patients With Inborn Errors of Immunity and Chronic Norovirus Infection.The Journal of infectious diseases · 2025Article
- Role of DOCK8 in cytokine storm syndromes.The Journal of allergy and clinical immunology · 2025Article
- Natural killer cells in skin: a unique opportunity to better characterize the many facets of an overlooked secondary lymphoid organ.Frontiers in immunology · 2025Review
- DIAPH1-Deficiency is Associated with Major T, NK and ILC Defects in Humans.Journal of clinical immunology · 2024Article
- β-Actin G342D as a Cause of NK Cell Deficiency Impairing Lytic Synapse Termination.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Unraveling the dynamic mechanisms of natural killer cells in viral infections: insights and implications.Virology journal · 2024Review
- Case report: Advanced age at transplantation and pre-emptive treatment with dupilumab in DOCK8 deficiency.Frontiers in immunology · 2024Article
- Hem1 inborn errors of immunity: waving goodbye to coordinated immunity in mice and humans.Frontiers in immunology · 2024Review
- Infections in Inborn Errors of Immunity with Combined Immune Deficiency: A Review.Pathogens (Basel, Switzerland) · 2023Review
- Immunity to Cryptosporidium: Lessons from Acquired and Primary Immunodeficiencies.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Hemophagocytic Lymphohistiocytosis Gene Variants in Multisystem Inflammatory Syndrome in Children.Biology · 2022Article
- Inhibition of SHP-1 activity by PKC-θ regulates NK cell activation threshold and cytotoxicity.eLife · 2022Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 7 institutions in 3 countries.
Funding
Abstract
backgroundDedicator of cytokinesis 8 (DOCK8) mutations are responsible for a rare primary combined immunodeficiency syndrome associated with severe cutaneous viral infections, increased IgE levels, autoimmunity, and malignancy. Natural killer (NK) cells are essential for tumor surveillance and defense against virally infected cells. NK cell function relies on Wiskott-Aldrich syndrome protein for filamentous actin (F-actin) accumulation at the lytic NK cell immunologic synapse. DOCK8 activates cell division cycle 42, which, together with Wiskott-Aldrich syndrome protein, coordinates F-actin reorganization. Although abnormalities in T- and B-cell function have been described in DOCK8-deficient patients, the role of NK cells in this disease is unclear.
objectivesWe sought to understand the role of DOCK8 in NK cell function to determine whether NK cell abnormalities explain the pathogenesis of the clinical syndrome of DOCK8 deficiency.
methodsA cohort of DOCK8-deficient patients was assembled, and patients' NK cells, as well as NK cell lines with stably reduced DOCK8 expression, were studied. NK cell cytotoxicity, F-actin content, and lytic immunologic synapse formation were measured.
resultsDOCK8-deficient patients' NK cells and DOCK8 knockdown cell lines all had decreased NK cell cytotoxicity, which could not be restored after IL-2 stimulation. Importantly, DOCK8 deficiency impaired F-actin accumulation at the lytic immunologic synapse without affecting overall NK cell F-actin content.
conclusionsDOCK8 deficiency results in severely impaired NK cell function because of an inability to form a mature lytic immunologic synapse through targeted synaptic F-actin accumulation. This defect might underlie and explain important attributes of the DOCK8 deficiency clinical syndrome, including the unusual susceptibility to viral infection and malignancy.
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