Journal article

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

CELL REPORTS | CELL PRESS | Published : 2015

Abstract

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 pro..

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Grants

Awarded by NHMRC Australia Fellowship


Awarded by NHMRC program grants


Awarded by NHMRC IRIISS grant


Funding Acknowledgements

The authors thank Liam Town, Joanne Sutton, and Kate Elder for the care and maintenance of the mouse colonies. We thank Fiona Amante, Marcela Montes De Oca, Christian Engwerda, and Fares Al-Ejeh for their technical and scientific help. M.J.S. is supported by a NHMRC Australia Fellowship (628623). L.M. is supported by the ARC Cancer Research Foundation. D.S.H. was supported by a NHMRC Career Development Fellowship. The project was supported by NHMRC program grants (1013667 and 1016647) and project grants (1044392, 1049407, 1066770, and 1057852) and was supported in part by an NHMRC IRIISS grant 361646 and a Victorian State Government Operational Infrastructure Scheme grant.