ArticleFrontiers in immunology2013
Inhibitory receptor signaling destabilizes immunological synapse formation in primary NK cells.
Article in Frontiers in immunology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 11 citations in OpenAlex.
- TCF19 drives a broad transcriptional program that potentiates optimal innate and adaptive functions of antiviral NK cells.Nature immunology · 2025Article
- Human natural killer cells: Form, function, and development.The Journal of allergy and clinical immunology · 2023Review
- Peptide: MHC-based DNA vaccination strategy to activate natural killer cells by targeting killer cell immunoglobulin-like receptors.Journal for immunotherapy of cancer · 2021Article
- Review
- Advanced Materials and Devices for the Regulation and Study of NK Cells.International journal of molecular sciences · 2019Review
- PD-1 blocks lytic granule polarization with concomitant impairment of integrin outside-in signaling in the natural killer cell immunological synapse.The Journal of allergy and clinical immunology · 2018Article
- Actin retrograde flow controls natural killer cell response by regulating the conformation state of SHP-1.The EMBO journal · 2018Article
- NK cell education via nonclassical MHC and non-MHC ligands.Cellular & molecular immunology · 2017Review
- The Planar Lipid Bilayer System Serves as a Reductionist Approach for Studying NK Cell Immunological Synapses and Their Functions.Methods in molecular biology (Clifton, N.J.) · 2016Article
- Imaging of Cell-Cell Communication in a Vertical Orientation Reveals High-Resolution Structure of Immunological Synapse and Novel PD-1 Dynamics.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- NK cells after transplantation: friend or foe.Immunologic research · 2014Review
- Molecular mechanisms regulating cytotoxic lymphocyte development and function, and their associations to human diseases.Frontiers in immunology · 2014Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Upon engagement of their cognate class I major histocompatibility complex ligands, receptors containing immunotyrosine-based inhibitory motifs (ITIMs) transduce signals that block cytolytic and inflammatory responses. In this manner, ITIM-coupled receptors play a crucial role in maintaining natural killer (NK) cell tolerance toward normal, healthy tissue. A number of studies, mostly using immortalized NK cell lines, have demonstrated that ITIM signaling functions by disrupting the cytolytic immunological synapse formed between an NK cell and its target. However, more recent imaging experiments using primary NK cells have suggested that inhibitory receptor engagement does not antagonize contact formation, casting doubt on the hypothesis that ITIM signals destabilize the synapse. To resolve this issue, we analyzed primary NK cell activation and contact formation on supported lipid bilayers containing controlled combinations of activating and inhibitory ligands. Under these conditions, we observed that ITIM signaling clearly inhibited adhesion, cell arrest, and calcium influx, three hallmarks of synapse formation. These results are consistent with previous reports showing that inhibitory receptors deliver a "reverse stop" signal, and confirm that ITIM signaling functions at least in part by destabilizing cytolytic synapse formation.
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