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Circadian rhythm reprogramming during lung inflammation.

Jeffrey A Haspel1, Sukrutha Chettimada1, Rahamthulla S Shaik1

  • 1Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02215, USA.

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Summary
This summary is machine-generated.

Acute illness reshapes circadian rhythms in the lungs, altering immune cell oscillations. This study reveals inflammation-induced changes in molecular and cellular rhythms during endotoxemia, impacting early lung injury.

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Area of Science:

  • Immunology
  • Chronobiology
  • Molecular Biology

Background:

  • Circadian rhythms regulate immune responses in healthy states.
  • Systemic inflammation during acute illness can disrupt clock gene expression.
  • The persistence and nature of circadian rhythms in illness remain poorly understood.

Purpose of the Study:

  • To investigate circadian gene and metabolite expression in the lungs during endotoxemia.
  • To understand how inflammation alters cellular and molecular circadian rhythms.
  • To determine the role of Bmal1 in inflammation-induced circadian changes.

Main Methods:

  • Genome-wide analysis of gene and metabolite expression in endotoxemic mouse lungs.
  • Analysis of leukocyte counts and cell type oscillations.
  • Investigation of Bmal1-dependent mechanisms.

Main Results:

  • Novel cellular and molecular circadian rhythms are elicited in endotoxemic lungs.
  • Endotoxin induces an endotoxin-specific circadian program with unique gene and metabolite profiles.
  • Circadian rhythms of lung leukocytes shift, with granulocytes dominating over lymphocytes in a Bmal1-dependent manner.

Conclusions:

  • Inflammation significantly reorganizes cellular and molecular circadian rhythms.
  • These re-organized rhythms are relevant to the early stages of lung injury.
  • Circadian regulation of immune responses is altered during acute inflammatory conditions.