Stem Cell Reports
Stem Cell Reports
5 years ago

Activated Tissue-Resident Mesenchymal Stromal Cells Regulate Natural Killer Cell Immune and Tissue-Regenerative Function

Activated Tissue-Resident Mesenchymal Stromal Cells Regulate Natural Killer Cell Immune and Tissue-Regenerative Function
The interaction of mesenchymal stromal cells (MSCs) with natural killer (NK) cells is traditionally thought of as a static inhibitory model, whereby resting MSCs inhibit NK cell effector function. Here, we use a dynamic in vitro system of poly(I:C) stimulation to model the interaction of NK cells and tissue-resident MSCs in the context of infection or tissue injury. The experiments suggest a time-dependent system of regulation and feedback, where, at early time points, activated MSCs secrete type I interferon to enhance NK cell effector function, while at later time points TGF-β and IL-6 limit NK cell effector function and terminate inflammatory responses by induction of a regulatory senescent-like NK cell phenotype. Importantly, feedback of these regulatory NK cells to MSCs promotes survival, proliferation, and pro-angiogenic properties. Our data provide additional insight into the interaction of stromal cells and innate immune cells and suggest a model of time-dependent MSC polarization and licensing.

Graphical abstract

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Teaser

Brandau et al. stimulated MSCs of the nasal mucosa with poly(I:C), a compound which mimics viral RNA. Although resting MSCs are thought to inhibit NK cell function, stimulated MSCs exerted a time-dependent biphasic response, which either promoted NK cell effector function (early response) or induced a senescent-like process (late response). The data suggest a model of time-dependent MSC polarization and innate immune interaction.

Publisher URL: www.sciencedirect.com/science

DOI: S2213671117302837

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