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

被引:48
作者
Nath, Pulak Ranjan [1 ]
Gangaplara, Arunakumar [2 ]
Pal-Nath, Dipasmita [1 ]
Mandal, Ajeet [3 ,4 ]
Maric, Dragan [5 ]
Sipes, John M. [1 ]
Cam, Maggie [3 ,4 ]
Shevach, Ethan M. [2 ]
Roberts, David D. [1 ]
机构
[1] NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA
[2] NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA
[3] NCI, CCR Collaborat Bioinformat Resource, Off Sci & Technol Resources, Bethesda, MD 20892 USA
[4] Leidos Biomed Res Inc, NIH, Bethesda, MD 20892 USA
[5] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA
来源
FRONTIERS IN IMMUNOLOGY | 2018年 / 9卷
关键词
CD47; natural killer cells; antisense morpholino; mouse models; viral immunity; lymphocytic choriomeningitis virus; transcriptome analysis; RNA-seq; ALPHA SIRP-ALPHA; NK CELLS; T-CELLS; MEDIATED ACTIVATION; ANTITUMOR-ACTIVITY; DENDRITIC CELLS; RECEPTORS; MICE; THROMBOSPONDIN-1; MATURATION;
D O I
10.3389/fimmu.2018.02985
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-alpha. 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.
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页数:15
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