NK cells at the interface between innate and adaptive immunity

In recent years a novel concept has emerged indicating that the actual role of natural killer (NK) cells is not confined to the
destruction of virus-infected cells or tumors. Indeed, different NK subsets exist that display major functional differences in their
cytolytic activity, cytokine production and homing capabilities. In particular, CD56high CD16- NK cells that largely predominate in
lymph nodes, have little cytolytic activity but release high levels of cytokines whereas CD56low CD16+ NK cells that predominate
in peripheral blood and inflamed tissues, display lower cytokine production, but potent cytotoxicity. The latter is characterized by
granule polarization and exocytosis of various proteins including perforin and granzymes that mediate target cell killing. The
recruitment of CD56low CD16+ NK cells into inflamed peripheral tissues is orchestrated by various chemochines including the
newly identified Chemerin. At these sites, NK cells, upon engagement of different triggering receptors become activated and
upregulate their cytokine production and cytotoxicity after interaction with myeloid dendritic cells (DCs). Importantly, during this
interaction NK cells also mediate the ‘editing’ of DCs undergoing maturation. This process appears to play a crucial role in
shaping both innate and adaptive immune responses. Indeed, only DCs undergoing this NK-mediated quality control would
become fully mature and capable of inducing priming of protective Th1 responses