ArticleCell2014
The RAG recombinase dictates functional heterogeneity and cellular fitness in natural killer cells.
Article in Cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
110 citing papers in PubMed, 171 citations in OpenAlex.
- PD-L1 is an intrinsic switch for natural killer cell-mediated, TRAIL-dependent antiviral function.Cell reports · 2026Article
- Peptide-adaptive NK cell memory in the absence of functional TCR genes.ImmunoHorizons · 2026Article
- One-step knock-in CAR constructs in human NK cells enable scalable, TGFβ1-resistant immunotherapy for solid tumors.Theranostics · 2026Article
- RAG1 deficiency durably alters dermal group 2 innate lymphoid cells and modifies contact hypersensitivity.Frontiers in immunology · 2026Article
- Recombination between fragile regions associated with chromosomal rearrangements in glioblastoma can be mediated by RAGs.iScience · 2025Article
- Conserved functional features of natural killer cell subsets in chicken, human, and murine immune systems.iScience · 2025Article
- Review
- RAG suppresses group 2 innate lymphoid cells.eLife · 2025Article
- Adaptive immune cells antagonize ILC2 homeostasis via SLAMF3 and SLAMF5.Science advances · 2025Article
- RAG recombinase expression discriminates the development of natural killer cells.Frontiers in immunology · 2025Article
- Efficient generation of human NOTCH ligand-expressing haemogenic endothelial cells as infrastructure for in vitro haematopoiesis and lymphopoiesis.Nature communications · 2024Article
- Fasting reshapes tissue-specific niches to improve NK cell-mediated anti-tumor immunity.Immunity · 2024Article
- Distinct developmental pathways generate functionally distinct populations of natural killer cells.Nature immunology · 2024Article
- Genetically corrected RAG2-SCID human hematopoietic stem cells restore V(D)J-recombinase and rescue lymphoid deficiency.Blood advances · 2024Article
- Transplantation after CD45-ADC corrects Rag1 immunodeficiency in congenic and haploidentical settings.The Journal of allergy and clinical immunology · 2024Article
- Hyperactive Natural Killer cells in Rag2 knockout mice inhibit the development of acute myeloid leukemia.Communications biology · 2023Article
- Parallel origins and functions of T cells and ILCs.Clinical and experimental immunology · 2023Review
- Unwinding the Role of the CMG Helicase in Inborn Errors of Immunity.Journal of clinical immunology · 2023Article
- Lymphoid cell development from fetal hematopoietic progenitors and human pluripotent stem cells.Immunological reviews · 2023Review
- Genomic Profiling of Lower-Grade Gliomas Subtype with Distinct Molecular and Clinicopathologic Characteristics via Altered DNA-Damage Repair Features.Journal of molecular neuroscience : MN · 2023Article
50 more citing papers are in PubMed but not listed here.
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3 authors at 2 institutions in 1 country.
Funding
Abstract
The emergence of recombination-activating genes (RAGs) in jawed vertebrates endowed adaptive immune cells with the ability to assemble a diverse set of antigen receptor genes. In contrast, innate lymphocytes, such as natural killer (NK) cells, are not believed to require RAGs. Here, we report that NK cells unable to express RAGs or RAG endonuclease activity during ontogeny exhibit a cell-intrinsic hyperresponsiveness but a diminished capacity to survive following virus-driven proliferation, a reduced expression of DNA damage response mediators, and defects in the repair of DNA breaks. Evidence for this novel function of RAG has also been observed in T cells and innate lymphoid cells (ILCs), revealing an unexpected role for RAG proteins beyond V(D)J recombination. We propose that DNA cleavage events mediated by RAG endow developing adaptive and innate lymphocytes with a cellular "fitness" that safeguards their persistence later in life during episodes of rapid proliferation or cellular stress.
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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.