The circadian gene mPer2 regulates the daily rhythm of IFN-gamma

J Interferon Cytokine Res. 2006 Sep;26(9):645-9. doi: 10.1089/jir.2006.26.645.


Circadian and daily rhythms regulate many aspects of physiology and behavior. Although a growing number of studies suggest that circadian disruptions may render organisms more susceptible to infection and cancer, the molecular links between the circadian system and the immune system are largely unknown. Here we report that mice carrying a loss-of-function mutation in the Per2 gene, a key component of the molecular circadian clock, lacked the physiologic daily rhythm of interferon-gamma (IFN-gamma) mRNA and protein expression in the spleen. These observations were associated with a significant alteration in the expression of canonical clock genes. In addition, Per2 mutant mice failed to show a daily rhythm in IFN-gamma serum levels, which were significantly lower than those determined in wild-type mice during the early light period. These findings provide novel evidence for a direct circadian regulation of IFN-gamma, a critical cytokine modulating the immune response.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • ARNTL Transcription Factors
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Biological Clocks / physiology
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Circadian Rhythm / physiology*
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Perforin
  • Period Circadian Proteins
  • Pore Forming Cytotoxic Proteins / genetics
  • Pore Forming Cytotoxic Proteins / metabolism
  • RNA, Messenger / metabolism
  • Spleen / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • ARNTL Transcription Factors
  • Arntl protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Cycle Proteins
  • Membrane Glycoproteins
  • Nuclear Proteins
  • Per1 protein, mouse
  • Per2 protein, mouse
  • Period Circadian Proteins
  • Pore Forming Cytotoxic Proteins
  • RNA, Messenger
  • Transcription Factors
  • Perforin
  • Interferon-gamma