ArticleThe Journal of clinical investigation2011
IL-2 induces a WAVE2-dependent pathway for actin reorganization that enables WASp-independent human NK cell function.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 83 citations in OpenAlex.
- Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome.Science (New York, N.Y.) · 2013Trial
- Rapamycin/IL-2 combination therapy in patients with type 1 diabetes augments Tregs yet transiently impairs β-cell function.Diabetes · 2012Trial
- Clinical, immunologic, and genetic characteristics of 148 patients with natural killer cell deficiency.The Journal of allergy and clinical immunology · 2025Article
- Micro Immune Response On-chip (MIRO) models the tumour-stroma interface for immunotherapy testing.Nature communications · 2025Article
- β-Actin G342D as a Cause of NK Cell Deficiency Impairing Lytic Synapse Termination.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Interleukin signaling in the regulation of natural killer cells biology in breast cancer.Frontiers in immunology · 2024Review
- NgR1 is an NK cell inhibitory receptor that destabilizes the immunological synapse.Nature immunology · 2023Article
- Partial loss-of-function mutations in GINS4 lead to NK cell deficiency with neutropenia.JCI insight · 2022Article
- Actin Retrograde Flow Regulated by the Wiskott-Aldrich Syndrome Protein Drives the Natural Killer Cell Response.Cancers · 2022Article
- Locked and Loaded: Mechanisms Regulating Natural Killer Cell Lytic Granule Biogenesis and Release.Frontiers in immunology · 2022Review
- Cereblon regulates NK cell cytotoxicity and migration via Rac1 activation.European journal of immunology · 2021Article
- Constitutive activation of WASp leads to abnormal cytotoxic cells with increased granzyme B and degranulation response to target cells.JCI insight · 2021Article
- The Role of the Cytoskeleton in Regulating the Natural Killer Cell Immune Response in Health and Disease: From Signaling Dynamics to Function.Frontiers in cell and developmental biology · 2021Review
- Filamin A Is Required for NK Cell Cytotoxicity at the Expense of Cytokine ProductionFrontiers in immunology · 2021Article
- Biomechanics of T Cell Dysfunctions in Chronic Diseases.Frontiers in immunology · 2021Review
- Higher Incidence of B Cell Malignancies in Primary Immunodeficiencies: A Combination of Intrinsic Genomic Instability and Exocytosis Defects at the Immunological Synapse.Frontiers in immunology · 2020Review
- Loss of ARPC1B impairs cytotoxic T lymphocyte maintenance and cytolytic activity.The Journal of clinical investigation · 2019Article
- KIR2DL4-HLAG interaction at human NK cell-oligodendrocyte interfaces regulates IFN-γ-mediated effects.Molecular immunology · 2019Article
- Article
- Activation of compensatory pathways via Rac2 in the absence of the Cdc42 effector Wiskott-Aldrich syndrome protein in Dendritic cells.Small GTPases · 2019Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency associated with an increased susceptibility to herpesvirus infection and hematologic malignancy as well as a deficiency of NK cell function. It is caused by defective WAS protein (WASp). WASp facilitates filamentous actin (F-actin) branching and is required for F-actin accumulation at the NK cell immunological synapse and NK cell cytotoxicity ex vivo. Importantly, the function of WASp-deficient NK cells can be restored in vitro after exposure to IL-2, but the mechanisms underlying this remain unknown. Using a WASp inhibitor as well as cells from patients with WAS, we have defined a direct effect of IL-2 signaling upon F-actin that is independent of WASp function. We found that IL-2 treatment of a patient with WAS enhanced the cytotoxicity of their NK cells and the F-actin content at the immunological synapses formed by their NK cells. IL-2 stimulation of NK cells in vitro activated the WASp homolog WAVE2, which was required for inducing WASp-independent NK cell function, but not for baseline activity. Thus, WAVE2 and WASp define parallel pathways to F-actin reorganization and function in human NK cells; although WAVE2 was not required for NK cell innate function, it was accessible through adaptive immunity via IL-2. These results demonstrate how overlapping cytoskeletal activities can utilize immunologically distinct pathways to achieve synonymous immune function.
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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.