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Front. Immunol. | doi: 10.3389/fimmu.2018.02985

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

  • 1National Institutes of Health (NIH), United States

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.
Cd47-/- 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 Cd47-/- NK cells exhibited increased expression of NK effector and
interferon gene signatures and an increased proliferative response to interleukin-15 in
vitro. Cd47-/- 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 Cd47-/- 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.

Keywords: CD47 role, Natural killer cells (NK cells), Antisense morpholino oligonucleotide, mouse models, viral immunity, Lymphocytic choriomeningitis virus (LCMV), transcriptome analysis, RNA-Seq

Received: 21 Aug 2018; Accepted: 04 Dec 2018.

Edited by:

Laurent Brossay, Brown University, United States

Reviewed by:

Stephen N. Waggoner, Cincinnati Children's Hospital Medical Center, United States
Sandeep K. Tripathy, Washington University in St. Louis, United States  

Copyright: © 2018 Nath, Gangaplara, Maric, Mandal, Cam, Roberts and Shevach. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. David D. Roberts, National Institutes of Health (NIH), Bethesda, 9000, Maryland, United States, droberts@mail.nih.gov