RESUMEN
Natural killer (NK) cells are bone-marrow-derived lymphocytes that play a crucial role in host defense against some viral and bacterial infections, as well as against tumors. Their phenotypic and functional maturation requires intimate interactions between the bone marrow stroma and committed precursors. In parallel to the identification of several phenotypic and functional stages of NK cell development, recent studies have shed new light on the role of stromal cells in driving functional maturation of NK cells. In this review, we provide an overview of the role of bone marrow microenvironment in NK cell differentiation.
Asunto(s)
Diferenciación Celular/fisiología , Células Asesinas Naturales/citología , Células del Estroma/fisiología , Animales , Antígenos CD34 , Médula Ósea/fisiología , Antígeno CD56 , Células Cultivadas , Citotoxicidad Inmunológica , Humanos , Interleucina-15 , Células Asesinas Naturales/fisiología , Ratones , Transducción de Señal , Células Madre/citología , Células Madre/fisiologíaRESUMEN
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.