High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF3

Dominic Francis De Nardo; Larisa I Labzin; Hajime Kono; Reiko Seki; Susanne Vicktoria Schmidt; Marc Beyer; Dakang Xu; Sebastian Zimmer; Catharina Lahrmann; Frank Alexander Schildberg; Johanna Vogelhuber; Michael Kraut; Thomas Ulas; Anja Kerksiek; Wolfgang Krebs; Niklas Bode; Alena Grebe; Michael L Fitzgerald; Nicholas J Hernandez; Bryan Raymond George Williams; Percy A Knolle; Manfred Kneilling; Martin Rocken; Dieter Lutjohann; Samuel D Wright; Joachim L Schultze; Eicke Latz

doi:10.1038/ni.2784

High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF3

Dominic Francis De Nardo, Larisa I Labzin, Hajime Kono, Reiko Seki, Susanne Vicktoria Schmidt, Marc Beyer, Dakang Xu, Sebastian Zimmer, Catharina Lahrmann, Frank Alexander Schildberg, Johanna Vogelhuber, Michael Kraut, Thomas Ulas, Anja Kerksiek, Wolfgang Krebs, Niklas Bode, Alena Grebe, Michael L Fitzgerald, Nicholas J Hernandez, Bryan Raymond George WilliamsPercy A Knolle, Manfred Kneilling, Martin Rocken, Dieter Lutjohann, Samuel D Wright, Joachim L Schultze, Eicke Latz

Hudson Institute - Department of Molecular and Translational Science

Research output: Contribution to journal › Article › Research › peer-review

343 Citations (Scopus)

Abstract

High-density lipoprotein (HDL) mediates reverse cholesterol transport and is known to be protective against atherosclerosis. In addition, HDL has potent anti-inflammatory properties that may be critical for protection against other inflammatory diseases. The molecular mechanisms of how HDL can modulate inflammation, particularly in immune cells such as macrophages, remain poorly understood. Here we identify the transcriptional regulator ATF3, as an HDL-inducible target gene in macrophages that downregulates the expression of Toll-like receptor (TLR)-induced proinflammatory cytokines. The protective effects of HDL against TLR-induced inflammation were fully dependent on ATF3 in vitro and in vivo. Our findings may explain the broad anti-inflammatory and metabolic actions of HDL and provide the basis for predicting the success of new HDL-based therapies.

Original language	English
Pages (from-to)	152 - 160
Number of pages	9
Journal	Nature Immunology
Volume	15
Issue number	2
DOIs	https://doi.org/10.1038/ni.2784
Publication status	Published - 2014

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De Nardo, D. F., Labzin, L. I., Kono, H., Seki, R., Schmidt, S. V., Beyer, M., Xu, D., Zimmer, S., Lahrmann, C., Schildberg, F. A., Vogelhuber, J., Kraut, M., Ulas, T., Kerksiek, A., Krebs, W., Bode, N., Grebe, A., Fitzgerald, M. L., Hernandez, N. J., ... Latz, E. (2014). High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF3. Nature Immunology, 15(2), 152 - 160. https://doi.org/10.1038/ni.2784

@article{948533451dae4d0398dff84ba5e68cf1,

title = "High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF3",

abstract = "High-density lipoprotein (HDL) mediates reverse cholesterol transport and is known to be protective against atherosclerosis. In addition, HDL has potent anti-inflammatory properties that may be critical for protection against other inflammatory diseases. The molecular mechanisms of how HDL can modulate inflammation, particularly in immune cells such as macrophages, remain poorly understood. Here we identify the transcriptional regulator ATF3, as an HDL-inducible target gene in macrophages that downregulates the expression of Toll-like receptor (TLR)-induced proinflammatory cytokines. The protective effects of HDL against TLR-induced inflammation were fully dependent on ATF3 in vitro and in vivo. Our findings may explain the broad anti-inflammatory and metabolic actions of HDL and provide the basis for predicting the success of new HDL-based therapies.",

author = "{De Nardo}, {Dominic Francis} and Labzin, {Larisa I} and Hajime Kono and Reiko Seki and Schmidt, {Susanne Vicktoria} and Marc Beyer and Dakang Xu and Sebastian Zimmer and Catharina Lahrmann and Schildberg, {Frank Alexander} and Johanna Vogelhuber and Michael Kraut and Thomas Ulas and Anja Kerksiek and Wolfgang Krebs and Niklas Bode and Alena Grebe and Fitzgerald, {Michael L} and Hernandez, {Nicholas J} and Williams, {Bryan Raymond George} and Knolle, {Percy A} and Manfred Kneilling and Martin Rocken and Dieter Lutjohann and Wright, {Samuel D} and Schultze, {Joachim L} and Eicke Latz",

year = "2014",

doi = "10.1038/ni.2784",

language = "English",

volume = "15",

pages = "152 -- 160",

journal = "Nature Immunology",

issn = "1529-2908",

publisher = "Nature Publishing Group",

number = "2",

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De Nardo, DF, Labzin, LI, Kono, H, Seki, R, Schmidt, SV, Beyer, M, Xu, D, Zimmer, S, Lahrmann, C, Schildberg, FA, Vogelhuber, J, Kraut, M, Ulas, T, Kerksiek, A, Krebs, W, Bode, N, Grebe, A, Fitzgerald, ML, Hernandez, NJ, Williams, BRG, Knolle, PA, Kneilling, M, Rocken, M, Lutjohann, D, Wright, SD, Schultze, JL & Latz, E 2014, 'High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF3', Nature Immunology, vol. 15, no. 2, pp. 152 - 160. https://doi.org/10.1038/ni.2784

TY - JOUR

T1 - High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF3

AU - De Nardo, Dominic Francis

AU - Labzin, Larisa I

AU - Kono, Hajime

AU - Seki, Reiko

AU - Schmidt, Susanne Vicktoria

AU - Beyer, Marc

AU - Xu, Dakang

AU - Zimmer, Sebastian

AU - Lahrmann, Catharina

AU - Schildberg, Frank Alexander

AU - Vogelhuber, Johanna

AU - Kraut, Michael

AU - Ulas, Thomas

AU - Kerksiek, Anja

AU - Krebs, Wolfgang

AU - Bode, Niklas

AU - Grebe, Alena

AU - Fitzgerald, Michael L

AU - Hernandez, Nicholas J

AU - Williams, Bryan Raymond George

AU - Knolle, Percy A

AU - Kneilling, Manfred

AU - Rocken, Martin

AU - Lutjohann, Dieter

AU - Wright, Samuel D

AU - Schultze, Joachim L

AU - Latz, Eicke

PY - 2014

Y1 - 2014

N2 - High-density lipoprotein (HDL) mediates reverse cholesterol transport and is known to be protective against atherosclerosis. In addition, HDL has potent anti-inflammatory properties that may be critical for protection against other inflammatory diseases. The molecular mechanisms of how HDL can modulate inflammation, particularly in immune cells such as macrophages, remain poorly understood. Here we identify the transcriptional regulator ATF3, as an HDL-inducible target gene in macrophages that downregulates the expression of Toll-like receptor (TLR)-induced proinflammatory cytokines. The protective effects of HDL against TLR-induced inflammation were fully dependent on ATF3 in vitro and in vivo. Our findings may explain the broad anti-inflammatory and metabolic actions of HDL and provide the basis for predicting the success of new HDL-based therapies.

AB - High-density lipoprotein (HDL) mediates reverse cholesterol transport and is known to be protective against atherosclerosis. In addition, HDL has potent anti-inflammatory properties that may be critical for protection against other inflammatory diseases. The molecular mechanisms of how HDL can modulate inflammation, particularly in immune cells such as macrophages, remain poorly understood. Here we identify the transcriptional regulator ATF3, as an HDL-inducible target gene in macrophages that downregulates the expression of Toll-like receptor (TLR)-induced proinflammatory cytokines. The protective effects of HDL against TLR-induced inflammation were fully dependent on ATF3 in vitro and in vivo. Our findings may explain the broad anti-inflammatory and metabolic actions of HDL and provide the basis for predicting the success of new HDL-based therapies.

UR - http://www.nature.com/ni/journal/v15/n2/pdf/ni.2784.pdf

U2 - 10.1038/ni.2784

DO - 10.1038/ni.2784

M3 - Article

SN - 1529-2908

VL - 15

SP - 152

EP - 160

JO - Nature Immunology

JF - Nature Immunology

IS - 2

ER -

High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF3

Abstract

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