Study Reveals Circadian Control of Immune Variability

In laboratory models, researchers at The University of Texas MD Anderson Cancer Center discovered that a mother's circadian rhythms, or internal body clock, can influence the immune system states of her offspring, which can accurately predict the risk of bacterial infection.

These findings offer novel insights into non-genetic factors shaping immune defenses and provide a framework to study circadian rhythms as a possible reason why some patients might be more vulnerable to getting infections during disease treatment. The study, published in Science Advances, was led by Alejandro Aballay, Ph.D., professor of Genetics and dean of the UTHealth Houston Graduate School of Biomedical Sciences.

These findings reveal a circadian mechanism that can create significant differences in infection outcomes even when genetics and environment are similar. This circadian control may help explain why patients with comparable risk profiles often experience very different responses to infection."

Alejandro Aballay, Ph.D., professor of Genetics and dean of the UTHealth Houston Graduate School of Biomedical Sciences

What are the Focus and Key Findings of This Study on the Immune System?

Many patients respond differently to treatments, highlighting a need to understand factors that can affect the immune system and make individuals more susceptible to infections. Various factors, such as genetics, epigenetics and the environment, can affect individual risk and severity of infections.

The researchers used fluorescent reporters to study biomarkers in the immune system of the C. elegans model before and after bacterial infection. Despite being almost genetically identical, these organisms can have very different immune responses – even in the same environment. This concept, called phenotypic heterogeneity, could help identify possible factors that can affect traits beyond genetics or environment.

The researchers found that some models with higher baseline expression of an inflammation biomarker were more susceptible to infection, and they identified key targets in the pathway that regulates that expression.

Interestingly, they noticed that maternal circadian rhythms were a factor that heavily influenced baseline expression levels of an inflammation biomarker. Interfering with genes involved in this internal clock eliminated that influence, suggesting that this is a significant source of immune variability.

What Significance Do These Findings Have for Patients?

These findings provide evidence that circadian rhythms can affect immune variability, suggesting that non-genetic factors can shape immune defenses. This raises questions about how internal clocks and other non-genetic factors can contribute to immune diversity in humans.

These findings suggest that this may be a reason why some patients react differently to treatments, even though they might be genetically similar. While further research is needed, exploring the circadian regulation of the C. elegans model can help understand the broader implications for personalized medicine and disease prevention strategies in humans.