TY - JOUR
T1 - The receptors CD96 and CD226 oppose each other in the regulation of natural killer cell functions
AU - Chan, Christopher J.
AU - Martinet, Ludovic
AU - Gilfillan, Susan
AU - Souza-Fonseca-Guimaraes, Fernando
AU - Chow, Melvyn T.
AU - Town, Liam
AU - Ritchie, David S.
AU - Colonna, Marco
AU - Andrews, Daniel M.
AU - Smyth, Mark J.
N1 - Funding Information:
We thank D. Godfrey (University of Melbourne) for CD1d tetramer loaded with α-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).
PY - 2014/5
Y1 - 2014/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84899099175&partnerID=8YFLogxK
U2 - 10.1038/ni.2850
DO - 10.1038/ni.2850
M3 - Article
C2 - 24658051
AN - SCOPUS:84899099175
SN - 1529-2908
VL - 15
SP - 431
EP - 438
JO - Nature immunology
JF - Nature immunology
IS - 5
ER -