The receptors CD96 and CD226 oppose each other in the regulation of natural killer cell functions

Chan, Christopher J., Martinet, Ludovic, Gilfillan, Susan, Souza-Fonseca-Guimaraes, Fernando, Chow, Melvyn T., Town, Liam, Ritchie, David S., Colonna, Marco, Andrews, Daniel M. and Smyth, Mark J. (2014) The receptors CD96 and CD226 oppose each other in the regulation of natural killer cell functions. Nature Immunology, 15 5: 431-438. doi:10.1038/ni.2850


Author Chan, Christopher J.
Martinet, Ludovic
Gilfillan, Susan
Souza-Fonseca-Guimaraes, Fernando
Chow, Melvyn T.
Town, Liam
Ritchie, David S.
Colonna, Marco
Andrews, Daniel M.
Smyth, Mark J.
Title The receptors CD96 and CD226 oppose each other in the regulation of natural killer cell functions
Journal name Nature Immunology   Check publisher's open access policy
ISSN 1529-2908
1529-2916
Publication date 2014-01-01
Year available 2014
Sub-type Article (original research)
DOI 10.1038/ni.2850
Volume 15
Issue 5
Start page 431
End page 438
Total pages 8
Place of publication New York, NY United States
Publisher Nature Publishing Group
Language eng
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 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
 
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