ArticleJournal of immunology (Baltimore, Md. : 1950)2016
NK Cell Maturation and Cytotoxicity Are Controlled by the Intramembrane Aspartyl Protease SPPL3.
Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 2 of them syntheses that pooled it.
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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
13 citing papers in PubMed, 2 syntheses or guidelines pooled it, 26 citations in OpenAlex.
- Common variants on 6q16.2, 12q24.31 and 16p13.3 are associated with major depressive disorder.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Pooled it
- Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis.Nature genetics · 2018Pooled it
- QRICH1 mediates an intracellular checkpoint for CD8Science immunology · 2025Article
- Genome-Wide Identification of the SPP/SPPL Gene Family andInternational journal of molecular sciences · 2024Article
- Pathogenesis of allergic diseases and implications for therapeutic interventions.Signal transduction and targeted therapy · 2023Review
- N-terminome analyses underscore the prevalence of SPPL3-mediated intramembrane proteolysis among Golgi-resident enzymes and its role in Golgi enzyme secretion.Cellular and molecular life sciences : CMLS · 2022Article
- Downregulation of Three Novel miRNAs in the Lymph Nodes of Sheep Immunized With theFrontiers in veterinary science · 2022Article
- Methylation of Immune-Related Genes in Peripheral Blood Leukocytes and Breast Cancer.Frontiers in oncology · 2022Article
- Genetics and Epigenetics in Allergic Rhinitis.Genes · 2021Review
- Article
- Oxidized CaMKII and O-GlcNAcylation cause increased atrial fibrillation in diabetic mice by distinct mechanisms.The Journal of clinical investigation · 2021Article
- Physiological functions of SPP/SPPL intramembrane proteases.Cellular and molecular life sciences : CMLS · 2020Review
- Signaling Functions of Intramembrane Aspartyl-Proteases.Frontiers in cardiovascular medicine · 2020Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
NK cell maturation is critical for normal effector function and the innate immune response to tumors and pathogens. However, the molecular pathways that control NK cell maturation remain largely undefined. In this article, we investigate the role of SPPL3, an intramembrane aspartyl protease, in murine NK cell biology. We find that deletion of SPPL3 in the hematopoietic system reduces numbers of peripheral NK cells, clearance of MHC class I-deficient tumors in vivo, and cytotoxicity against tumor cells in vitro. This phenotype is concomitant with reduced numbers of CD27(+)CD11b(+) and CD27(-)CD11b(+) NK cells, indicating a requirement for SPPL3 in efficient NK cell maturation. NK cell-specific deletion of SPPL3 results in the same deficiencies, revealing a cell-autonomous role for SPPL3 in these processes. CRISPR/Cas9 genomic editing in murine zygotes was used to generate knockin mice with a catalytically compromised SPPL3 D271A allele. Mice engineered to express only SPPL3 D271A in NK cells phenocopy mice deleted for SPPL3, indicating a requirement for SPPL3 protease activity in NK cell biology. Our results identify SPPL3 as a cell-autonomous molecular determinant of NK cell maturation and expand the role of intramembrane aspartyl proteases in innate immunity.
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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.