‘Timekeeper’ shapes body’s infection defenses, UTSW study finds
Adrenaline receptor sets T cells’ internal clock, regulates antiviral response
DALLAS – Sept. 3, 2025 – A newly discovered “timekeeper” for fighting infections dramatically shapes the body’s immune defenses, offering insight as to why antiviral T cell response varies throughout the day, according to UT Southwestern Medical Center researchers. Their findings, published in Science Advances, could lead to new strategies for treating infections, using immunotherapies to combat cancer, and limiting the effects of body clock disruptors such as jet lag and shift work.
The scientists found that a protein on the surface of T cells that binds to adrenaline appears to act as a timekeeper for the cells’ infection-fighting function. This pathway suppresses inflammation while also increasing vulnerability to disease. The discovery could help explain why individuals might be more susceptible to some infections or experience more severe symptoms at various times during a 24-hour period.
“The adrenaline receptor sets the internal clock of virus-specific T cells, which regulates how well 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. Dr. Farrar co-led the study with Drashya Sharma, Ph.D., Instructor of Immunology at UTSW.
Most organisms have biological functions that cycle on a 24-hour time frame, a phenomenon known as circadian rhythm. For humans and many other mammals, light sets these cycles by programming a region of the brain that sends chemical signals throughout the body to synchronize the circadian clocks in cells, tissues, and organs.
Although scientists have long known the immune system functions on its own daily cycle – for example, vaccines tend to elicit a greater immune response when given in the morning than at night – it has not been known which chemical signals regulate its circadian clock.
Dr. Farrar and his colleagues got their first clues in a study they published in 2022. To better understand the role of the adrenaline receptor on T cells, they used genetic engineering to remove this receptor (ADRB2) from T cell surfaces. Surprisingly, among more than 300 genes affected by this change, the researchers found several genes important for maintaining circadian rhythms.
In the new study, Drs. Farrar and Sharma and their colleagues discovered that deleting ADRB2 had an inconsistent effect on these circadian clock genes. While some lost their rhythmic expression, others adopted abnormal rhythms, either shifting when they were normally expressed within a 24-hour cycle or cycling outside a 24-hour period.
Next, healthy, normal mice and others genetically altered to remove ADRB2 from their T cells were infected with vesicular stomatitis virus, a common pathogen for this species. T cells of the mice with ADRB2 proliferated and differentiated into various subsets, as typically happens after exposure to bacterial and viral pathogens; however, T cells of the mice lacking ADRB2 had reduced proliferation and differentiation.
One subset particularly affected in the altered mice was memory T cells, which are targeted by vaccines. These cells stick around after infection, preserving a cellular memory of the pathogen so they can launch a new attack upon exposure to the same pathogen in the future.
Drs. Farrar and Sharma explained that adrenaline produced by brain cells rises upon waking and falls at bedtime, a cycle that’s the opposite of immune activity. Because some circadian clock genes in T cells continue to cycle even in the absence of ADRB2, the researchers added, adrenaline is probably just one of several chemical signals that direct circadian rhythms in T cells.
Future research in the Farrar Lab will focus on identifying other cycle-setting chemicals in these immune cells as well as how they affect T cell response to various pathogens at different times of the day.
Other UTSW researchers who contributed to this study include Kira Kohlbach, A.S., Research Assistant II; and Robert Maples, B.S., graduate student researcher. This research was funded by grants from the National Institutes of Health (AI175217, AI143248, and AI125545), and the Beecherl Endowment of UT Southwestern Medical Center.
About UT Southwestern Medical Center
UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 24 members of the National Academy of Sciences, 23 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 140,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5.1 million outpatient visits a year.