Nature Immunology 7, 747 - 754 (2006)
Published online: 4 June 2006; | doi:10.1038/ni1353
Natural killer cell differentiation driven by Tyro3 receptor tyrosine kinasesAnouk Caraux1, 5, Qingxian Lu2, 5, Nadine Fernandez3, Sylvain Riou4, James P Di Santo1, David H Raulet3, Greg Lemke2
& Claude Roth41
Laboratoire Cytokines et développement Lymphoïde, Département d'Immunologie, Institut Pasteur, 75724 Paris Cedex 15, France. 2
Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, California 92037, USA. 3
Department of Molecular and Cell Biology and Cancer Research Laboratory, University of California, Berkeley, California 94720-3200, USA. 4
Laboratoire Immunité Cellulaire Antivirale, Département d'Immunologie, Institut Pasteur, 75724 Paris Cedex 15, France. 5
These authors contributed equally to this work.
Correspondence should be addressed to Claude Roth clroth@pasteur.fr Although understanding of the function and specificity of many natural killer (NK) cell receptors is increasing, the molecular mechanisms regulating their expression during late development of NK cells remain unclear. Here we use representational difference analysis to identify molecules required for late NK cell differentiation. Axl protein tyrosine kinase, together with the structurally related receptors Tyro3 and Mer, were essential for NK cell functional maturation and normal expression of inhibitory and activating NK cell receptors. Also, all three receptors were expressed in maturing NK cells, the ligands of these receptors were produced by bone marrow stromal cells, and recombinant versions of these ligands drove NK cell differentiation in vitro. These results collectively suggest that Axl, Tyro3 and Mer transmit signals that are essential for the generation of a functional NK cell repertoire.
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