Natural Killer (NK) cells confer protection from tumors and infections by releasing cytotoxic granules and pro-inflammatory cytokines upon recognition of diseased cells. The responsiveness of NK cells to acute stimulation is dynamically tuned by steady-state receptor-ligand interactions of an NK cell with its cellular environment. Here we demonstrate that in healthy WT mice the NK activating receptor NKG2D is engaged in vivo by one of its ligands, RAE-1ε, which is expressed constitutively by lymph node endothelial cells and highly induced on tumor-associated endothelium. This interaction causes internalization of NKG2D from the NK cell surface and transmits an NK-intrinsic signal that desensitizes NK cell responses globally to acute stimulation, resulting in impaired NK anti-tumor responses in vivo.
- David H Raulet
- David H Raulet
- Thornton W Thompson
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All mice were maintained at the University of California, Berkeley and experiments were conducted in accordance with approved protocols from the Animal Care and Use Committee, under protocol number AUP-2015-10-8058.
- Wayne M Yokoyama, Reviewing Editor, Howard Hughes Medical Institute, Washington University School of Medicine, United States
© 2017, Thompson et al.
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