title: Microfluidic-based, live-cell analysis allows assessment of NK-cell migration in response to crosstalk with dendritic cells.
abstract: Migration and localization of NK cells into peripheral tissues are tightly regulated under normal and pathological conditions. The physiological importance of NK cell-DC crosstalk has been well documented. However, the ways in which DCs regulate the migratory properties of NK cells (such as chemotaxis, chemokinesis, chemo-repulsion) are not fully defined in vitro. Here, we employed a microfluidic platform to examine, at the single-cell level, C57BL/6 NK-cell migrations in a stable chemical gradient. We observed that soluble factors released by the immature and LPS-activated mature DCs induced a high level of chemotactic movement of IL-2-activated NK cells in vitro. We confirmed these findings in a standard trans-well migration assay, and identified CXCR3 as a key receptor on the NK cells that mediated the migration. More interestingly, we revealed a novel function of granulocyte macrophage colony-stimulating factor in repulsing NK-cell migrations. The future uses of such microfluidic device in the systematic evaluations of NK-cell migratory responses in NK cell-DC crosstalk will provide new insights into the development of DC-based NK-cell therapies against tumor and infections.
authors: Department of Immunology, University of Manitoba, Winnipeg, MB, Canada.
authors: Sajid
authors: S
authors: Mahmood
authors: Saravanan
authors: S
authors: Nandagopal
authors: Ibrahim
authors: I
authors: Sow
authors: Francis
authors: F
authors: Lin
authors: Sam K P
authors: SK
authors: Kung
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D046210:Microfluidic Analytical Techniques
chemical_list: D000970:Antineoplastic Agents; D007376:Interleukin-2; D008070:Lipopolysaccharides
keywords: Bone marrow-derived dendritic cells; Chemo-repulsion; Chemotaxis; Microfluidic device; NK-DC crosstalk; Natural killer cell