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ATF3 regulates MCMV infection in mice by modulating IFN-γ expression in natural killer cells

ATF3 regulates MCMV infection in mice by modulating IFN-γ expression in natural killer cells Activating transcription factor 3 (ATF3) is a negative regulator of proinflammatory cytokine expression in macrophages, and ATF3-deficient mice are more susceptible to endotoxic shock. Here, we demonstrate that ATF3 interacts with a cis-regulatory element of the IFN-γ gene in natural killer (NK) cells, and that ATF3null NK cells show increased transcription and secretion of IFN-γ. NK cell-derived IFN-γ has previously been demonstrated to be protective against murine cytomegalovirus (MCMV) infection, and we show here that ATF3null mice exhibit decreased hepatic viral load and reduced liver histopathology upon challenge with MCMV. Reconstitution of NK-deficient mice with ATF3null NK cells more effectively controlled MCMV infection than mice reconstituted with WT cells, indicating that ATF3 acts within NK cells to regulate antiviral responses. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Proceedings of the National Academy of Sciences PNAS

ATF3 regulates MCMV infection in mice by modulating IFN-γ expression in natural killer cells

ATF3 regulates MCMV infection in mice by modulating IFN-γ expression in natural killer cells

Proceedings of the National Academy of Sciences , Volume 105 (7): 2544 – Feb 19, 2008

Abstract

Activating transcription factor 3 (ATF3) is a negative regulator of proinflammatory cytokine expression in macrophages, and ATF3-deficient mice are more susceptible to endotoxic shock. Here, we demonstrate that ATF3 interacts with a cis-regulatory element of the IFN-γ gene in natural killer (NK) cells, and that ATF3null NK cells show increased transcription and secretion of IFN-γ. NK cell-derived IFN-γ has previously been demonstrated to be protective against murine cytomegalovirus (MCMV) infection, and we show here that ATF3null mice exhibit decreased hepatic viral load and reduced liver histopathology upon challenge with MCMV. Reconstitution of NK-deficient mice with ATF3null NK cells more effectively controlled MCMV infection than mice reconstituted with WT cells, indicating that ATF3 acts within NK cells to regulate antiviral responses.

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Publisher
PNAS
Copyright
Copyright ©2009 by the National Academy of Sciences
ISSN
0027-8424
eISSN
1091-6490
Publisher site
See Article on Publisher Site

Abstract

Activating transcription factor 3 (ATF3) is a negative regulator of proinflammatory cytokine expression in macrophages, and ATF3-deficient mice are more susceptible to endotoxic shock. Here, we demonstrate that ATF3 interacts with a cis-regulatory element of the IFN-γ gene in natural killer (NK) cells, and that ATF3null NK cells show increased transcription and secretion of IFN-γ. NK cell-derived IFN-γ has previously been demonstrated to be protective against murine cytomegalovirus (MCMV) infection, and we show here that ATF3null mice exhibit decreased hepatic viral load and reduced liver histopathology upon challenge with MCMV. Reconstitution of NK-deficient mice with ATF3null NK cells more effectively controlled MCMV infection than mice reconstituted with WT cells, indicating that ATF3 acts within NK cells to regulate antiviral responses.

Journal

Proceedings of the National Academy of SciencesPNAS

Published: Feb 19, 2008

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