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Circadian rhythm reprogramming during lung inflammation

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  • Jeffrey A. Haspel

    (Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02215, USA
    Present address: Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, Campus Box 8052, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA)

  • Sukrutha Chettimada

    (Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02215, USA)

  • Rahamthulla S. Shaik

    (Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02215, USA)

  • Jen-Hwa Chu

    (Brigham and Women’s Hospital, 181 Longwood Avenue, Boston, Massachusetts 02215, USA)

  • Benjamin A. Raby

    (Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02215, USA
    Brigham and Women’s Hospital, 181 Longwood Avenue, Boston, Massachusetts 02215, USA)

  • Manuela Cernadas

    (Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02215, USA)

  • Vincent Carey

    (Brigham and Women’s Hospital, 181 Longwood Avenue, Boston, Massachusetts 02215, USA)

  • Vanessa Process

    (Brigham and Women’s Hospital, 181 Longwood Avenue, Boston, Massachusetts 02215, USA)

  • G. Matthew Hunninghake

    (Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02215, USA)

  • Emeka Ifedigbo

    (Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02215, USA)

  • James A. Lederer

    (Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02215, USA)

  • Joshua Englert

    (Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02215, USA)

  • Ashley Pelton

    (Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02215, USA)

  • Anna Coronata

    (Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02215, USA)

  • Laura E. Fredenburgh

    (Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02215, USA)

  • Augustine M.K. Choi

    (New York Presbyterian/Weill Cornell Medical Center, 555 East 68 Street, New York, New York, 10065, USA)

Abstract

Circadian rhythms are known to regulate immune responses in healthy animals, but it is unclear whether they persist during acute illnesses where clock gene expression is disrupted by systemic inflammation. Here we use a genome-wide approach to investigate circadian gene and metabolite expression in the lungs of endotoxemic mice and find that novel cellular and molecular circadian rhythms are elicited in this setting. The endotoxin-specific circadian programme exhibits unique features, including a divergent group of rhythmic genes and metabolites compared with the basal state and a distinct periodicity and phase distribution. At the cellular level, endotoxin treatment also alters circadian rhythms of leukocyte counts within the lung in a bmal1-dependent manner, such that granulocytes rather than lymphocytes become the dominant oscillating cell type. Our results show that inflammation produces a complex re-organization of cellular and molecular circadian rhythms that are relevant to early events in lung injury.

Suggested Citation

  • Jeffrey A. Haspel & Sukrutha Chettimada & Rahamthulla S. Shaik & Jen-Hwa Chu & Benjamin A. Raby & Manuela Cernadas & Vincent Carey & Vanessa Process & G. Matthew Hunninghake & Emeka Ifedigbo & James A, 2014. "Circadian rhythm reprogramming during lung inflammation," Nature Communications, Nature, vol. 5(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5753
    DOI: 10.1038/ncomms5753
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    Cited by:

    1. Qixin Wang & Isaac Kirubakaran Sundar & Joseph H. Lucas & Jun-Gyu Park & Aitor Nogales & Luis Martinez-Sobrido & Irfan Rahman, 2023. "Circadian clock molecule REV-ERBα regulates lung fibrotic progression through collagen stabilization," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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