TY - JOUR TI - Endothelial cells express NKG2D ligands and desensitize antitumor NK responses AU - Thompson, Thornton W AU - Kim, Alexander Byungsuk AU - Li, P Jonathan AU - Wang, Jiaxi AU - Jackson, Benjamin T AU - Huang, Kristen Ting Hui AU - Zhang, Lily AU - Raulet, David H A2 - Yokoyama, Wayne M VL - 6 PY - 2017 DA - 2017/12/12 SP - e30881 C1 - eLife 2017;6:e30881 DO - 10.7554/eLife.30881 UR - https://doi.org/10.7554/eLife.30881 AB - 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 antitumor responses in vivo. KW - Natural killer cells KW - endothelial cells KW - NKG2D JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -