CD47 expression in natural killer cell regulates homeostasis and modulates immune response to lymphocytic choriomeningitis virus. CD47 expression in natural killer cell regulates homeostasis and modulates immune response to lymphocytic choriomeningitis virus

CD47 is a ubiquitous cell surface receptor that limits cell clearance by phagocytes that express its counter-receptor signal-regulatory protein-α and directly regulates T cell immunity by interacting with its inhibitory ligand thrombospondin-1. Murine natural killer (NK) cells express higher levels of CD47 than other lymphocytes, but the role of CD47 in regulating NK cell homeostasis and immune function remains unclear. Cd47-/- mice exhibited depletion of NK precursors in bone marrow, but antisense Cd47 knockdown or gene disruption resulted in a dose dependent accumulation of immature and mature NK cells in spleen. Cd47-/- mice were impaired in controlling chronic Clone-13 lymphocytic choriomeningitis virus (LCMV) infection, which was associated with depletion of splenic NK cells and loss of effector cytokine and interferon response gene expression in Cd47-/- NK cells. These data identify CD47 as a cell-intrinsic and systemic regulator of NK cell homeostasis and NK cell responses to viral infection. Overall design: Examining natural killer (NK) cell intrinsic role of CD47 during viral infection.