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Gene-specific control of inflammation by TLR-induced chromatin modifications

Author

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  • Simmie L. Foster

    (Yale University School of Medicine, New Haven, Connecticut 06405, USA)

  • Diana C. Hargreaves

    (Yale University School of Medicine, New Haven, Connecticut 06405, USA)

  • Ruslan Medzhitov

    (Yale University School of Medicine, New Haven, Connecticut 06405, USA)

Abstract

Toll-like receptors (TLRs) induce a multi-component inflammatory response that must be tightly regulated to avoid tissue damage. Most known regulatory mechanisms target TLR signalling pathways and thus broadly inhibit multiple aspects of the inflammatory response. Given the functional diversity of TLR-induced genes, we proposed that additional, gene-specific regulatory mechanisms exist to allow individual aspects of the TLR-induced response to be differentially regulated. Using an in vitro system of lipopolysaccharide tolerance in murine macrophages, we show that TLR-induced genes fall into two categories on the basis of their functions and regulatory requirements. We demonstrate that representatives from the two classes acquire distinct patterns of TLR-induced chromatin modifications. These gene-specific chromatin modifications are associated with transient silencing of one class of genes, which includes pro-inflammatory mediators, and priming of the second class, which includes antimicrobial effectors. These findings illustrate an adaptive response in macrophages and reveal component-specific regulation of inflammation.

Suggested Citation

  • Simmie L. Foster & Diana C. Hargreaves & Ruslan Medzhitov, 2007. "Gene-specific control of inflammation by TLR-induced chromatin modifications," Nature, Nature, vol. 447(7147), pages 972-978, June.
    • Handle: RePEc:nat:nature:v:447:y:2007:i:7147:d:10.1038_nature05836
    DOI: 10.1038/nature05836
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    Cited by:

    1. Raphael Watt & Kimberley Parkin & David Martino, 2020. "The Potential Effects of Short-Chain Fatty Acids on the Epigenetic Regulation of Innate Immune Memory," Challenges, MDPI, vol. 11(2), pages 1-16, October.
    2. Patricia Severino & Eliézer Silva & Giovana Lotici Baggio-Zappia & Milena Karina Coló Brunialti & Laura Alejandra Nucci & Otelo Rigato Jr. & Ismael Dale Cotrim Guerreiro da Silva & Flávia Ribeiro Mach, 2014. "Patterns of Gene Expression in Peripheral Blood Mononuclear Cells and Outcomes from Patients with Sepsis Secondary to Community Acquired Pneumonia," PLOS ONE, Public Library of Science, vol. 9(3), pages 1-8, March.

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