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

Research output: Contribution to journalArticleResearchpeer-review

212 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 languageEnglish
Pages (from-to)152 - 160
Number of pages9
JournalNature Immunology
Volume15
Issue number2
DOIs
Publication statusPublished - 2014

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