Journal article
The receptors CD96 and CD226 oppose each other in the regulation of natural killer cell functions
CJ Chan, L Martinet, S Gilfillan, F Souza-Fonseca-Guimaraes, MT Chow, L Town, DS Ritchie, M Colonna, DM Andrews, MJ Smyth
Nature Immunology | Published : 2014
DOI: 10.1038/ni.2850
Abstract
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 knowled..
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Grants
Awarded by National Institute of Arthritis and Musculoskeletal and Skin Diseases
Funding Acknowledgements
We thank D. Godfrey (University of Melbourne) for CD1d tetramer loaded with alpha-galactosylceramide; J. Sutton and K. Elder for the care and maintenance of the mouse colonies. Supported by the Leukaemia Foundation of Australia (C. J. C.), the Monash University Faculty of Medicine (C. J. C.), the National Health and Medical Research Council (D. M. A. and M. J. S.; 1013667, 1044392 and 628623) and the US National Institutes of Health (P30AR048335 for the Speed Congenics Facility of the Rheumatic Diseases Core Center at the Washington University School of Medicine).