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In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells
Published on: September 28, 2017
The circadian gene mPer2 regulates the daily rhythm of IFN-gamma
Alvaro Arjona1, Dipak K Sarkar
1Endocrine Program and Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901, USA.
Abstract:
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.
Insights
The circadian system directly regulates interferon-gamma (IFN-gamma) production. Loss of the Per2 gene disrupts daily rhythms of IFN-gamma, impacting immune response and potentially increasing susceptibility to disease.
Area of Science:
- Immunology
- Chronobiology
- Molecular Biology
Background:
- Circadian and daily rhythms govern physiological processes and behavior.
- Circadian disruptions are linked to increased susceptibility to infection and cancer.
- Molecular links between the circadian and immune systems remain largely unknown.
Purpose of the Study:
- To investigate the molecular connection between the circadian clock and immune response.
- To determine the role of the Per2 gene in regulating daily rhythms of immune factors.
Main Methods:
- Utilized Per2 mutant mice lacking a functional molecular circadian clock.
- Measured daily rhythms of interferon-gamma (IFN-gamma) mRNA and protein expression in spleen.
- Assessed serum levels of IFN-gamma and expression of canonical clock genes.
Main Results:
- Per2 mutant mice exhibited a lack of daily rhythm in splenic IFN-gamma mRNA and protein.
- Mutant mice showed altered expression of core circadian clock genes.
- IFN-gamma serum levels lacked daily rhythm and were lower in Per2 mutant mice compared to wild-type.
Conclusions:
- The Per2 gene is crucial for the circadian regulation of IFN-gamma production.
- These findings reveal a direct link between the circadian system and a key immune cytokine.
- Disruption of circadian rhythms may impair immune function through altered IFN-gamma regulation.
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