ArticleJCI insight2017
DOCK8 enforces immunological tolerance by promoting IL-2 signaling and immune synapse formation in Tregs.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 43 citations in OpenAlex.
- Emerging Paediatric Uses of Dupilumab Beyond Approvals.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2026Review
- Pediatric DOCK8 Deficiency Beyond Infections and Atopy: An Immunoactinopathy with Immune Dysregulation and Multisystem Involvement.Children (Basel, Switzerland) · 2026Article
- Comprehensive Profiling of T- and B-Cell Receptor Repertoires Demonstrates Impaired Developmental and Activation of Adaptive Immunity in DOCK8 Deficiency.Journal of clinical immunology · 2026Article
- Loss of the actin remodeling protein Flightless-1 impairs CD8 and regulatory T cell function.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- DOCK8 and STAT3 cooperate to restrain IgE-inducing T follicular helper cells.The Journal of experimental medicine · 2026Article
- Dock8 regulates Th2 cell differentiation through ANXA1.Fundamental research · 2026Article
- DOCK8 in immune cells: roles and mechanisms.Frontiers in immunology · 2026Review
- Biomechanical signaling of cytoskeleton and membrane reorganization in tumor immune chemotactic migration.Theranostics · 2026Review
- Comprehensive αβ T-Cell Receptor Repertoire Analysis Reveals a Unique CD8+ TCR Landscape in DOCK8-Deficient Patients.Allergy · 2025Article
- Immunological synapse: structures, molecular mechanisms and therapeutic implications in disease.Signal transduction and targeted therapy · 2025Review
- Establish TIIC signature score based the machine learning fusion in bladder cancer.Discover oncology · 2024Article
- Metabolic fitness of IgAMucosal immunology · 2024Article
- Insights into the pathogenesis of allergic disease from dedicator of cytokinesis 8 deficiency.Current opinion in immunology · 2023Review
- CRISPR/Cas-Based Gene Editing Strategies for DOCK8 Immunodeficiency Syndrome.Frontiers in genome editing · 2022Article
- Inborn Errors of the Immune System Associated With Atopy.Frontiers in immunology · 2022Review
- Deciphering the role of DOCK8 in tumorigenesis by regulating immunity and the application of nanotechnology in DOCK8 deficiency therapy.Frontiers in pharmacology · 2022Review
- Cutting Edge: DOCK8 Regulates a Subset of Dendritic Cells That Is Critical for the Development of Experimental Autoimmune Encephalomyelitis.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- DOCK8 Expression in Regulatory T Cells Maintains their Stability and Limits Contact Hypersensitivity.The Journal of investigative dermatology · 2021Article
- Case Report: Hypomorphic Function and Somatic Reversion in DOCK8 Deficiency in One Patient With Two Novel Variants and Sclerosing Cholangitis.Frontiers in immunology · 2021Article
- DOCK8 deficiency diminishes thymic T-regulatory cell development but not thymic deletion.Clinical & translational immunology · 2021Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Patients deficient in the guanine nucleotide exchange factor DOCK8 have decreased numbers and impaired in vitro function of Tregs and make autoantibodies, but they seldom develop autoimmunity. We show that, similarly, Dock8-/- mice have decreased numbers and impaired in vitro function of Tregs but do not develop autoimmunity. In contrast, mice with selective DOCK8 deficiency in Tregs develop lymphoproliferation, autoantibodies, and gastrointestinal inflammation, despite a normal percentage and in vitro function of Tregs, suggesting that deficient T effector cell function might protect DOCK8-deficient patients from autoimmunity. We demonstrate that DOCK8 associates with STAT5 and is important for IL-2-driven STAT5 phosphorylation in Tregs. DOCK8 localizes within the lamellar actin ring of the Treg immune synapse (IS). Dock8-/- Tregs have abnormal TCR-driven actin dynamics, decreased adhesiveness, an altered gene expression profile, an unstable IS with decreased recruitment of signaling molecules, and impaired transendocytosis of the costimulatory molecule CD86. These data suggest that DOCK8 enforces immunological tolerance by promoting IL-2 signaling, TCR-driven actin dynamics, and the IS in Tregs.
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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.