The receptors CD96 and CD226 oppose each other in the regulation of natural killer cell functions
Copyright policy )The receptors CD96 and CD226 oppose each other in the regulation of natural killer cell functions
CD96, CD226 (DNAM-1) and TIGIT belong to an emerging family of receptors that interact with nectin and nectin-like proteins. CD226 activates natural killer (NK) cell-mediated cytotoxicity, whereas TIGIT reportedly counterbalances CD226. In contrast, the role of CD96, which shares the ligand CD155 with CD226 and TIGIT, has remained unclear. In this study we found that CD96 competed with CD226 for CD155 binding and limited NK cell function by direct inhibition. As a result, Cd96(-/-) mice displayed hyperinflammatory responses to the bacterial product lipopolysaccharide (LPS) and resistance to carcinogenesis and experimental lung metastases. Our data provide the first description, to our knowledge, of the ability of CD96 to negatively control cytokine responses by NK cells. Blocking CD96 may have applications in pathologies in which NK cells are important.
- Peter MacCallum Cancer Centre Australia
- University of Mary United States
- QIMR Berghofer Medical Research Institute Australia
- University of Queensland Australia
- University of Queensland Australia
Antigens, Differentiation, T-Lymphocyte, Cytotoxicity, Immunologic, Lipopolysaccharides, Lung Neoplasms, Immunology, Nectins, Mice, Antigens, CD, Animals, Neoplasm Metastasis, Receptors, Immunologic, Cells, Cultured, Mice, Knockout, 2403 Immunology, T Lineage-Specific Activation Antigen 1, Neoplasms, Experimental, Pneumonia, Killer Cells, Natural, Mice, Inbred C57BL, Receptors, Virus, Cell Adhesion Molecules, Protein Binding
Antigens, Differentiation, T-Lymphocyte, Cytotoxicity, Immunologic, Lipopolysaccharides, Lung Neoplasms, Immunology, Nectins, Mice, Antigens, CD, Animals, Neoplasm Metastasis, Receptors, Immunologic, Cells, Cultured, Mice, Knockout, 2403 Immunology, T Lineage-Specific Activation Antigen 1, Neoplasms, Experimental, Pneumonia, Killer Cells, Natural, Mice, Inbred C57BL, Receptors, Virus, Cell Adhesion Molecules, Protein Binding
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