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

Stem Cell Reports. 2017 Sep 12;9(3):985-998. doi: 10.1016/j.stemcr.2017.06.020. Epub 2017 Aug 3.


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.

Keywords: Poly(I:C); TGF-β; TLR 3; mesenchymal stromal cell polarization; mucosal tissue; natural killer cell activation; senescence; type I interferon; viral infection.

MeSH terms

  • Apoptosis / drug effects
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism
  • Cell Communication / drug effects
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cellular Senescence / drug effects
  • Cytotoxicity, Immunologic / drug effects
  • Humans
  • Inflammation / pathology
  • Interleukin-6 / metabolism
  • Killer Cells, Natural / cytology*
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / metabolism
  • Lymphocyte Activation / drug effects
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Nasal Mucosa / cytology
  • Phenotype
  • Poly I-C / pharmacology
  • Receptors, CXCR4 / metabolism
  • Regeneration* / drug effects
  • Time Factors
  • Transforming Growth Factor beta / metabolism
  • Wound Healing / drug effects


  • Interleukin-6
  • Receptors, CXCR4
  • Transforming Growth Factor beta
  • Poly I-C