DNAM-1 Expression Marks an Alternative Program of NK Cell Maturation
Ludovic Martinet,
Lucas Ferrari De Andrade,
Camille Guillerey,
Jason S. Lee,
Jing Liu,
Fernando Souza-Fonseca-Guimaraes,
Dana S. Hutchinson,
Tatiana B. Kolesnik,
Sandra E. Nicholson,
Nicholas D. Huntington,
Mark J. Smyth
Affiliations
Ludovic Martinet
Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia
Lucas Ferrari De Andrade
Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia
Camille Guillerey
Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia
Jason S. Lee
Control of Gene Expression Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia
Jing Liu
Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia
Fernando Souza-Fonseca-Guimaraes
Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia
Dana S. Hutchinson
Department of Pharmacology, Drug Discovery Biology, Monash Institute of Pharmaceutical, Sciences, Monash University, 399 Royal Parade, Parkville, VIC 3052, Australia
Tatiana B. Kolesnik
The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3050, Australia
Sandra E. Nicholson
The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3050, Australia
Nicholas D. Huntington
The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3050, Australia
Mark J. Smyth
Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia
Natural killer (NK) cells comprise a heterogeneous population of cells important for pathogen defense and cancer surveillance. However, the functional significance of this diversity is not fully understood. Here, we demonstrate through transcriptional profiling and functional studies that the activating receptor DNAM-1 (CD226) identifies two distinct NK cell functional subsets: DNAM-1+ and DNAM-1− NK cells. DNAM-1+ NK cells produce high levels of inflammatory cytokines, have enhanced interleukin 15 signaling, and proliferate vigorously. By contrast, DNAM-1− NK cells that differentiate from DNAM-1+ NK cells have greater expression of NK-cell-receptor-related genes and are higher producers of MIP1 chemokines. Collectively, our data reveal the existence of a functional program of NK cell maturation marked by DNAM-1 expression.
