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, Augustine M.K. Choi

Research output: Contribution to journalArticle

61 Scopus citations

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.

Original languageEnglish (US)
Article number4753
JournalNature Communications
Volume5
DOIs
StatePublished - Sep 11 2014

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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