Journal Article

CD47 Expression in Natural Killer Cells Regulates Homeostasis and Modulates Immune Response to Lymphocytic Choriomeningitis Virus

Gangaplara, Arunakumar, Maric, Dragan, Pal-Nath, Dipasmita, Sipes, John M., Nath, Pulak Ranjan, Cam, Maggie, Shevach, Ethan M., Roberts, David D., Mandal, Ajeet

2018

Overview

CD47 is a ubiquitous cell surface receptor that directly regulates T cell immunity by interacting with its inhibitory ligand thrombospondin-1 and limits clearance of cells by phagocytes that express its counter-receptor signal-regulatory protein-α. 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. mice exhibited depletion of NK precursors in bone marrow, consistent with the antiphagocytic function of CD47. In contrast, antisense CD47 knockdown or gene disruption resulted in a dose dependent accumulation of immature and mature NK cells in spleen. Mature NK cells exhibited increased expression of NK effector and interferon gene signatures and an increased proliferative response to interleukin-15 . mice showed no defect in their early response to acute Armstrong lymphocytic choriomeningitis virus (LCMV) infection but were moderately impaired in controlling chronic Clone-13 LCMV infection, which was associated with depletion of splenic NK cells and loss of effector cytokine and interferon response gene expression in NK cells. Broad CD47-dependent differences in NK activation, survival, and exhaustion pathways were observed in NK cell transcriptional signatures in LCMV infected mice. These data identify CD47 as a cell-intrinsic and systemic regulator of NK cell homeostasis and NK cell function in responding to a viral infection.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Animals / Antibodies / Antigen presentation / antisense morpholino / Bacterial infections / Bone marrow / Bone Marrow Transplantation / CD47 / CD47 Antigen - genetics / CD47 Antigen - immunology / CD47 Antigen - metabolism / Cell culture / Cell growth / Cell Proliferation / Cell surface / Cell surface receptors / Chronic infection / Dendritic cells / Disease Models, Animal / Effector cells / Female / Gene disruption / Homeostasis / Humans / Immune clearance / Immune response / Immune system / Immunity (Disease) / Immunology / Interferon / Interleukin 15 / Killer Cells, Natural - immunology / Killer Cells, Natural - metabolism / Laboratory animals / Lymphocytes / Lymphocytes T / Lymphocytic Choriomeningitis - immunology / Lymphocytic Choriomeningitis - virology / lymphocytic choriomeningitis virus / Lymphocytic choriomeningitis virus - immunology / Male / Mice / Mice, Inbred C57BL / Mice, Knockout / mouse models / Natural killer cells / Osteoprogenitor cells / Phagocytes / Protocol / SHPS-1 protein / Spleen / Spleen - cytology / Spleen - immunology / T cell receptors / Thrombospondin / Transplantation Chimera / viral immunity / Viral infections