ArticleBlood2021
RhoG deficiency abrogates cytotoxicity of human lymphocytes and causes hemophagocytic lymphohistiocytosis.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 53 citations in OpenAlex.
- Implications of Rho GTPase signaling in cancer immunotherapy.Biochemical Society transactions · 2026Review
- Immune-related actinopathies at the cross-road of immunodeficiency, autoimmunity and autoinflammation.Nature reviews. Immunology · 2026Review
- Genetic and molecular approaches for patients with familial hemophagocytic lymphohistiocytosis: a multi-center experience from Mexico.Frontiers in immunology · 2026Article
- Boosting immune cells to combat cancer using CRISPR engineering and large-scale in vivo testing.Nature · 2025Article
- Article
- Clinical and prognostic significance of whole blood Epstein-Barr virus DNA in patients with primary hemophagocytic lymphohistiocytosis: a retrospective observational study from China.Annals of hematology · 2025Observational
- Promising Targeted Therapies for Hemophagocytic Lymphohistiocytosis: A Translational Perspective Based on Immunopathology.Clinical reviews in allergy & immunology · 2025Review
- Deep insight into cytokine storm: from pathogenesis to treatment.Signal transduction and targeted therapy · 2025Review
- Efficacy of T-cell assays for the diagnosis of primary defects in cytotoxic lymphocyte exocytosis.Blood · 2024Article
- Article
- β-Actin G342D as a Cause of NK Cell Deficiency Impairing Lytic Synapse Termination.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Functional role of UNC13D in immune diseases and its therapeutic applications.Frontiers in immunology · 2024Review
- Inborn Errors of Immunity and Cytokine Storm Syndromes.Advances in experimental medicine and biology · 2024Review
- CD8Advances in experimental medicine and biology · 2024Review
- Genetic background of primary and familial HLH in Qatar: registry data and population study.Frontiers in pediatrics · 2024Article
- NEDD8-activating enzyme inhibition potentiates the anti-myeloma activity of natural killer cells.Cell death & disease · 2023Article
- Role of RhoG as a regulator of cellular functions: integrating insights on immune cell activation, migration, and functions.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- Approaching hemophagocytic lymphohistiocytosis.Frontiers in immunology · 2023Review
- Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee.Journal of clinical immunology · 2022Article
- RhoG's Role in T Cell Activation and Function.Frontiers in immunology · 2022Review
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Authors and funding
24 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Exocytosis of cytotoxic granules (CG) by lymphocytes is required for the elimination of infected and malignant cells. Impairments in this process underly a group of diseases with dramatic hyperferritinemic inflammation termed hemophagocytic lymphohistiocytosis (HLH). Although genetic and functional studies of HLH have identified proteins controlling distinct steps of CG exocytosis, the molecular mechanisms that spatiotemporally coordinate CG release remain partially elusive. We studied a patient exhibiting characteristic clinical features of HLH associated with markedly impaired cytotoxic T lymphocyte (CTL) and natural killer (NK) cell exocytosis functions, who beared biallelic deleterious mutations in the gene encoding the small GTPase RhoG. Experimental ablation of RHOG in a model cell line and primary CTLs from healthy individuals uncovered a hitherto unappreciated role of RhoG in retaining CGs in the vicinity of the plasma membrane (PM), a fundamental prerequisite for CG exocytotic release. We discovered that RhoG engages in a protein-protein interaction with Munc13-4, an exocytosis protein essential for CG fusion with the PM. We show that this interaction is critical for docking of Munc13-4+ CGs to the PM and subsequent membrane fusion and release of CG content. Thus, our study illuminates RhoG as a novel essential regulator of human lymphocyte cytotoxicity and provides the molecular pathomechanism behind the identified here and previously unreported genetically determined form of HLH.
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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.