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CD47 Expression in Natural Killer Cells Regulates Homeostasis and Modulates Immune Response to Lymphocytic Choriomeningitis Virus
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 lev...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320676/ https://www.ncbi.nlm.nih.gov/pubmed/30643501 http://dx.doi.org/10.3389/fimmu.2018.02985 |
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author | Nath, Pulak Ranjan Gangaplara, Arunakumar Pal-Nath, Dipasmita Mandal, Ajeet Maric, Dragan Sipes, John M. Cam, Maggie Shevach, Ethan M. Roberts, David D. |
author_facet | Nath, Pulak Ranjan Gangaplara, Arunakumar Pal-Nath, Dipasmita Mandal, Ajeet Maric, Dragan Sipes, John M. Cam, Maggie Shevach, Ethan M. Roberts, David D. |
author_sort | Nath, Pulak Ranjan |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6320676 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-63206762019-01-14 CD47 Expression in Natural Killer Cells Regulates Homeostasis and Modulates Immune Response to Lymphocytic Choriomeningitis Virus Nath, Pulak Ranjan Gangaplara, Arunakumar Pal-Nath, Dipasmita Mandal, Ajeet Maric, Dragan Sipes, John M. Cam, Maggie Shevach, Ethan M. Roberts, David D. Front Immunol Immunology 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. Frontiers Media S.A. 2018-12-20 /pmc/articles/PMC6320676/ /pubmed/30643501 http://dx.doi.org/10.3389/fimmu.2018.02985 Text en Copyright © 2018 Nath, Gangaplara, Pal-Nath, Mandal, Maric, Sipes, Cam, Shevach and Roberts. http://creativecommons.org/licenses/by/4.0/ 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. |
spellingShingle | Immunology Nath, Pulak Ranjan Gangaplara, Arunakumar Pal-Nath, Dipasmita Mandal, Ajeet Maric, Dragan Sipes, John M. Cam, Maggie Shevach, Ethan M. Roberts, David D. CD47 Expression in Natural Killer Cells Regulates Homeostasis and Modulates Immune Response to Lymphocytic Choriomeningitis Virus |
title | CD47 Expression in Natural Killer Cells Regulates Homeostasis and Modulates Immune Response to Lymphocytic Choriomeningitis Virus |
title_full | CD47 Expression in Natural Killer Cells Regulates Homeostasis and Modulates Immune Response to Lymphocytic Choriomeningitis Virus |
title_fullStr | CD47 Expression in Natural Killer Cells Regulates Homeostasis and Modulates Immune Response to Lymphocytic Choriomeningitis Virus |
title_full_unstemmed | CD47 Expression in Natural Killer Cells Regulates Homeostasis and Modulates Immune Response to Lymphocytic Choriomeningitis Virus |
title_short | CD47 Expression in Natural Killer Cells Regulates Homeostasis and Modulates Immune Response to Lymphocytic Choriomeningitis Virus |
title_sort | cd47 expression in natural killer cells regulates homeostasis and modulates immune response to lymphocytic choriomeningitis virus |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320676/ https://www.ncbi.nlm.nih.gov/pubmed/30643501 http://dx.doi.org/10.3389/fimmu.2018.02985 |
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