Their findings, published in Science Advances, may pave the way for new approaches to infection treatment, cancer immunotherapy, and mitigating the impact of body clock disruptions like jet lag or shift work. The researchers identified a protein on T cell surfaces that interacts with adrenaline, acting as a “timekeeper” for the cells’ infection-fighting activity. This pathway both dampens inflammation and increases susceptibility to disease, potentially explaining why people may be more vulnerable to certain infections or experience more severe symptoms at different times of the day.

The adrenaline receptor controls the internal clock of virus-specific T cells, determining how effectively they respond to viral infections at different times of the day,” said David Farrar, Ph.D., Associate Professor of Immunology and Molecular Biology at UT Southwestern. He co-led the study with Drashya Sharma, Ph.D., Instructor of Immunology at UTSW.

Most living organisms exhibit biological processes that follow a roughly 24-hour cycle, known as the circadian rhythm. In humans and many other mammals, exposure to light sets these rhythms by influencing a brain region that sends chemical signals throughout the body, coordinating the circadian clocks in cells, tissues, and organs

Although it has long been recognized that the immune system follows its own daily cycle for instance, vaccines often trigger stronger responses in the morning than at night—the chemical signals governing this circadian rhythm remained unclear. Dr. Farrar and his team first explored this in a 2022 study and then investigated the role of the adrenaline receptor (ADRB2) on T cells by genetically removing it from their surfaces. Among more than 300 genes affected by this modification, several were crucial for maintaining circadian rhythms. In their latest study, the researchers found that deleting ADRB2 disrupted these clock genes in complex ways: some lost their normal rhythmic patterns, while others developed abnormal cycles, either shifting their usual timing within a 24-hour period or oscillating outside the typical daily cycle.

In experiments, healthy mice and genetically modified mice lacking ADRB2 on their T cells were infected with vesicular stomatitis virus, a common pathogen for this species. In normal mice, T cells proliferated and differentiated into various subsets as expected following infection, whereas T cells in ADRB2-deficient mice showed reduced proliferation and differentiation. Memory T cells a subset crucial for vaccines because they retain a cellular memory of pathogens to respond to future exposures were particularly affected. Drs. Farrar and Sharma noted that adrenaline levels, which rise upon waking and drop at bedtime, follow a cycle opposite to immune activity. Since some circadian clock genes in T cells continued to oscillate even without ADRB2, the researchers suggest that adrenaline is likely one of multiple chemical signals guiding T cell circadian rhythms.

Source: https://www.utsouthwestern.edu/newsroom/articles/year-2025/sept-adrenaline-receptor.html