Cutting edge: the AP-1 subunit JunB determines NK cell-mediated target cell killing by regulation of the NKG2D-ligand RAE-1epsilon.
The activating receptor NKG2D and its ligands RAE-1 play an important role in the NK, gammadelta+, and CD8+ T cell-mediated immune response to tumors. Expression levels of RAE-1 on target cells have to be tightly controlled to allow immune cell activation against tumors but to avoid destruction of healthy tissues. In this study, we report that cell surface expression of RAE-1epsilon is greatly enhanced on cells lacking JunB, a subunit of the transcription complex AP-1. Furthermore, tissue-specific junB knockout mice respond to 12-O-tetradecanoyl-phorbol-13-acetate, a potent AP-1 activator, with markedly increased and sustained epidermal RAE-1epsilon expression. Accordingly, junB-deficient cells are efficiently killed via NKG2D by NK cells and induce IFN-gamma production. Our data indicate that the transcription factor AP-1, which is involved in tumorigenesis and cellular stress responses, regulates RAE-1epsilon. Thus, up-regulated RAE-1epsilon expression due to low levels of JunB could alert immune cells to tumors and stressed cells.
Nausch
Norman
N
Division of Innate Immunity, German Cancer Research Center, Heidelberg, Germany.
Florin
Lore
L
Hartenstein
Bettina
B
Angel
Peter
P
Schorpp-Kistner
Marina
M
Cerwenka
Adelheid
A
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D055655:NK Cell Lectin-Like Receptor Subfamily K; D016133:Polymerase Chain Reaction; D011971:Receptors, Immunologic / Q000276:immunology*; D055607:Receptors, Natural Killer Cell; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000276:immunology*
D002273:Carcinogens; C527086:Klrk1 protein, mouse; D008024:Ligands; D008565:Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; C491219:Raet1a protein, mouse; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D018808:Transcription Factor AP-1; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate