Cytoskeletal stabilization of inhibitory interactions in immunologic synapses of mature human dendritic cells with natural killer cells

6533b833fe1ef96bd129c29d

RESEARCH PRODUCT

Cytoskeletal stabilization of inhibitory interactions in immunologic synapses of mature human dendritic cells with natural killer cells

Christian Münz Rosa Barreira Da Silva Rosa Barreira Da Silva Claudine Graf

subject

Immunological Synapses Immunology Cell Communication macromolecular substances Biochemistry Immunological synapse Natural killer cell 03 medical and health sciences 0302 clinical medicine Interleukin-15 Receptor alpha Subunit Microscopy Electron Transmission Receptors KIR MHC class I medicine Humans Antigen-presenting cell Cells Cultured Cytoskeleton 030304 developmental biology 0303 health sciences Microscopy Confocal biology Receptors Interleukin-12 Dendritic Cells Cell Biology Hematology Dendritic cell Flow Cytometry Interleukin-12 Immunological Synapses Actins Coculture Techniques 3. Good health Cell biology Killer Cells Natural medicine.anatomical_structure Microscopy Fluorescence biology.protein Interleukin 12 RNA Interference K562 Cells Microtubule-Organizing Center Wiskott-Aldrich Syndrome Protein 030215 immunology K562 cells

description

Abstract Human mature dendritic cells (DCs) can efficiently stimulate natural killer (NK)–cell responses without being targeted by their cytotoxicity. To understand this important regulatory crosstalk, we characterized the development of the immunologic synapse between mature DCs and resting NK cells. Conjugates between these 2 innate leukocyte populations formed rapidly, persisted for prolonged time periods and matured with DC-derived f-actin polymerization at the synapse. Polarization of IL-12 and IL-12R to the synapse coincided with f-actin polymerization, while other activating and inhibitory molecules were enriched at the interface between DCs and NK cells earlier. Functional assays revealed that inhibition of f-actin polymerization in mature synapses led to an increase of IFN-γ secretion and cytotoxicity by NK cells. This elevated NK-cell reactivity resulted from decreased inhibitory signaling in the absence of MHC class I polarization at the interface, which was observed on inhibition of f-actin polymerization in DCs. Thus, inhibitory signaling is stabilized by f-actin at the synapse between mature DCs and resting NK cells.

year	journal	country	edition	language
2011-09-16	Blood

https://doi.org/10.1182/blood-2011-07-366328