Human mesenchymal stromal/stem cells acquire immunostimulatory capacity upon cross-talk with natural killer cells and might improve the NK cell function of immunocompromised patients

Autor: Heike Rekasi, Sven Brandau, Rongtao Cui, Marcus Jäger, Robert Michael Petri, Monika Hepner-Schefczyk, Kai Fessmann, Kirsten Bruderek, Stefanie B. Flohé
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
Chemokine
Medizin
Mesenchymal stromal cells
Medicine (miscellaneous)
Injury
Cell Communication
Interleukin 21
Interferon gamma
Chemokine CCL2
Receptors
Interferon
Trauma Severity Indices
biology
Interleukin-18
Middle Aged
Natural killer T cell
Interleukin-12
Killer Cells
Natural
Interleukin 12
Molecular Medicine
Natural killer cells
Female
Stem cell
Chemokines
CCL2
medicine.drug
Adult
Receptors
CCR2
Biochemistry
Genetics and Molecular Biology (miscellaneous)
Trauma
Antibodies
Immunomodulation
03 medical and health sciences
Immunocompromised Host
Interferon-gamma
medicine
Humans
Lymphokine-activated killer cell
Multiple Trauma
Research
Mesenchymal stem cell
Mesenchymal Stem Cells
Cell Biology
Coculture Techniques
030104 developmental biology
Culture Media
Conditioned
Immunology
biology.protein
CCR2
Immunosuppression
MCP-1
Zdroj: Stem Cell Research & Therapy
ISSN: 1757-6512
Popis: Background The suppressive effect of mesenchymal stromal/stem cells (MSCs) on diverse immune cells is well known, but it is unclear whether MSCs additionally possess immunostimulatory properties. We investigated the impact of human MSCs on the responsiveness of primary natural killer (NK) cells in terms of cytokine secretion. Methods Human MSCs were generated from bone marrow and nasal mucosa. NK cells were isolated from peripheral blood of healthy volunteers or of immunocompromised patients after severe injury. NK cells were cultured with MSCs or with MSC-derived conditioned media in the absence or presence of IL-12 and IL-18. C-C chemokine receptor (CCR) 2, C-C chemokine ligand (CCL) 2, and the interferon (IFN)-γ receptor was blocked by specific inhibitors or antibodies. The synthesis of IFN-γ and CCL2 was determined. Results In the absence of exogenous cytokines, trace amounts of NK cell-derived IFN-γ licensed MSCs for enhanced synthesis of CCL2. In turn, MSCs primed NK cells for increased release of IFN-γ in response to IL-12 and IL-18. Priming of NK cells by MSCs occurred in a cell–cell contact-independent manner and was impaired by inhibition of the CCR2, the receptor of CCL2, on NK cells. CD56bright NK cells expressed higher levels of CCR2 and were more sensitive to CCL2-mediated priming by MSCs and by recombinant CCR2 ligands than cytotoxic CD56dim NK cells. NK cells from severely injured patients were impaired in cytokine-induced IFN-γ synthesis. Co-culture with MSCs or with conditioned media from MSCs and MSC/NK cell co-cultures from healthy donors improved the IFN-γ production of the patients’ NK cells in a CCR2-dependent manner. Conclusions A positive feedback loop driven by NK cell-derived IFN-γ and MSC-derived CCL2 increases the inflammatory response of cytokine-stimulated NK cells not only from healthy donors but also from immunocompromised patients. Therapeutic application of MSCs or their soluble factors might thus improve the NK function after severe injury.
Databáze: OpenAIRE
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