ArticleProceedings of the National Academy of Sciences of the United States of America2011
ORAI1-mediated calcium influx is required for human cytotoxic lymphocyte degranulation and target cell lysis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
123 citing papers in PubMed, 214 citations in OpenAlex.
- Article
- Targeting Reactive Species Stress and Nutrient Sensing to Enhance NK-Cell Function: Mechanistic Strategies for Overcoming Pancreatic Cancer Progression and Resistance Through Supplement Therapy.International journal of molecular sciences · 2026Review
- Stiff matrix impairs cytotoxic T lymphocyte function at multiple levels.Science advances · 2026Article
- Orai1 acts as a novel CaExperimental & molecular medicine · 2026Article
- A shear stress-responsive pathway in monocytes drives cardiopulmonary bypass-induced inflammation via spectrin/RAF1/store-operated calcium entry.Cell reports · 2026Article
- Conditional T and NK cell antagonism by a giant and highly conserved orthopoxvirus virulence factor.Research square · 2026Article
- Potassium channels as an ionic checkpoint in tumor immunity.Frontiers in pharmacology · 2026Review
- KCa3.1 channels regulate the tumor infiltration of functionally competent NK cells in head and neck cancer.Scientific reports · 2025Article
- A membrane lipid signature unravels the dynamic landscape of group 1 innate lymphoid cells across the health-disease continuum.iScience · 2025Article
- GzmkFrontiers in immunology · 2025Review
- Phenotypic Heterogeneity in ORAI-1-Associated Congenital Myopathy.Global medical genetics · 2024Article
- CaBiophysics reports · 2024Article
- Focusing on CD8Journal of experimental & clinical cancer research : CR · 2024Review
- Efficacy of T-cell assays for the diagnosis of primary defects in cytotoxic lymphocyte exocytosis.Blood · 2024Article
- Natural Killer Cell Mechanosensing in Solid Tumors.Bioengineering (Basel, Switzerland) · 2024Review
- Synthetic Biology Meets CaCells · 2024Review
- Benidipine impairs innate immunity converting sublethal to lethal infections in a murine model of spotted fever rickettsiosis.PLoS neglected tropical diseases · 2024Article
- The link between intracellular calcium signaling and exosomal PD-L1 in cancer progression and immunotherapy.Genes & diseases · 2024Review
- Reassessing granzyme B: unveiling perforin-independent versatility in immune responses and therapeutic potentials.Frontiers in immunology · 2024Review
- Regulation of anti-tumor immunity by metal ion in the tumor microenvironment.Frontiers in immunology · 2024Review
63 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 9 institutions in 5 countries.
Funding
Abstract
Lymphocytes mediate cytotoxicity by polarized release of the contents of cytotoxic granules toward their target cells. Here, we have studied the role of the calcium release-activated calcium channel ORAI1 in human lymphocyte cytotoxicity. Natural killer (NK) cells obtained from an ORAI1-deficient patient displayed defective store-operated Ca(2+) entry (SOCE) and severely defective cytotoxic granule exocytosis leading to impaired target cell lysis. Similar findings were obtained using NK cells from a stromal interaction molecule 1-deficient patient. The defect occurred at a late stage of the signaling process, because activation of leukocyte functional antigen (LFA)-1 and cytotoxic granule polarization were not impaired. Moreover, pharmacological inhibition of SOCE interfered with degranulation and target cell lysis by freshly isolated NK cells and CD8(+) effector T cells from healthy donors. In addition to effects on lymphocyte cytotoxicity, synthesis of the chemokine macrophage inflammatory protein-1β and the cytokines TNF-α and IFN-γ on target cell recognition was impaired in ORAI1-deficient NK cells, as previously described for T cells. By contrast, NK cell cytokine production induced by combinations of IL-12, IL-15, and IL-18 was not impaired by ORAI1 deficiency. Taken together, these results identify a critical role for ORAI1-mediated Ca(2+) influx in granule exocytosis for lymphocyte cytotoxicity as well as for cytokine production induced by target cell recognition.
Indexed as
Identifiers
What OpenQuestion holds
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.