Circadian rhythm reprogramming during lung inflammation

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. Lederer, Joshua Englert, Ashley Pelton, Anna Coronata, Laura E. Fredenburgh and Augustine M.K. Choi
Additional contact information
Jeffrey A. Haspel: Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02215, 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
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

Nature Communications, 2014, vol. 5, issue 1, 1-15

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms5753

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