Mutual activation of natural killer cells and monocytes mediated by NKp80-AICL interaction.
Receptors encoded by the natural killer (NK) cell gene complex (such as NKG2D) govern the reactivity of NK cells. However, the function and ligand(s) of the NK cell gene complex-encoded human NK cell receptor NKp80 remain elusive. Here we demonstrate that NKp80 binds to the genetically linked 'orphan' receptor AICL, which, like NKp80, is absent from rodents. We defined AICL as a myeloid-specific activating receptor that is upregulated by Toll-like receptor stimulation. AICL-NKp80 interactions promoted NK cell-mediated cytolysis of malignant myeloid cells. In addition, during crosstalk between NK cells and monocytes, NKp80 stimulated the release of proinflammatory cytokines from both cell types. Thus, by specifically bridging NK cells and myeloid cells, NKp80-AICL interactions may contribute to the initiation and maintenance of immune responses at sites of inflammation.
Welte
Stefan
S
Department of Immunology, Institute for Cell Biology, Eberhard Karls University of Tübingen, 72076 Tübingen, Germany.
Kuttruff
Sabrina
S
Waldhauer
Inja
I
Steinle
Alexander
A
D000818:Animals; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D006801:Humans; D015151:Immunoblotting; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D020239:Receptor Cross-Talk / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell; D020349:Surface Plasmon Resonance; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
C104778:CLEC2B protein, human; C431711:KLRF1 protein, human; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma