The human body’s circadian rhythm can significantly impact many biological processes, including, but not limited to, the efficacy and side effects associated with drug treatments; however, the molecular basis underlying the circadian control of human immune cells has remained difficult to verify due to the restrictions related to human data collection and the lack of in vivo human-specific study platforms. But this may all change thanks to a peer-reviewed paper, “Uncovering the Mystery of Opposite Circadian Rhythms between Mouse and Human Leukocytes in Humanized Mice” published by Zhao, et al in the August 2017 edition of Blood Journal.
According to their findings, humanized mice can carry and express both mouse and human immune cells and are “able to retain their own species-specific nature even though they are growing both cell types in the same environment”. The study also “proves that intracellular regulation mechanisms within mouse and human leukocytes, rather than extracellular factors, play more critical roles in determining how to traffic among different locations and generate circadian rhythm.”
In this novel study, rodent circulating leukocytes and hematopoietic progenitor cells showed the same circadian oscillation as heterozygous and wildtype (WT) mice, with peak circulation during the day, whereas human leukocytes exhibited opposite oscillations with peak trafficking and circulation overnight. These results followed similar circadian rhythm patterns previously observed in both humans and murine models in their natural host state and allowed Zhao, et al to specifically look at the mechanisms associated with controlling these processes.
Verification of the environmental and molecular parameters associated with the human circadian rhythm means that researchers can now begin to further investigate the impact and effectiveness of timed drug therapies as part of their preclinical studies, which many hope will lead to improved outcomes in the treatment of a variety of human diseases.