Adrenaline Receptor Regulates Daily Circadian Rhythm of T Cell Infection Response

Recent research from UT Southwestern Medical Center has uncovered a crucial 'timekeeper' mechanism that influences how the immune system responds to infections throughout the day. Scientists have identified a protein on the surface of T cells, known as the adrenaline receptor, which plays a vital role in regulating the cells' circadian rhythms—the biological processes that follow a 24-hour cycle. This discovery provides significant insight into why antiviral T cell responses vary depending on the time of day, a phenomenon previously observed but not fully understood.

The study, published in Science Advances, reveals that activation of the adrenaline receptor suppresses inflammation and modulates the immune response by acting as a key circadian regulator within T cells. Specifically, the receptor's engagement influences the expression of genes that control T cell activity, including those responsible for forming memory cells vital for long-term immunity.

Experiments involving genetically engineered mice lacking the adrenaline receptor demonstrated altered circadian gene expression and reduced effectiveness in fighting viral infections, such as vesicular stomatitis virus. These mice exhibited a decrease in T cell proliferation and differentiation, especially affecting memory T cells, which are essential for rapid response upon re-infection.

The findings suggest that adrenaline—a hormone produced by the brain in cycles that oppose immune activity—serves as one of several chemical signals guiding circadian regulation in T cells. This relationship could help explain fluctuations in infection severity and immune responsiveness based on the time of day, impacting strategies for vaccinations, immunotherapies, and managing disruptions caused by sleep disturbances or shift work.

Building on previous research where removing the receptor ADRB2 affected circadian gene patterns, the team plans to continue investigating other chemical signals that may influence immune cell clocks. Understanding these pathways could open new approaches to optimize immune responses and improve outcomes against infectious diseases and perhaps even cancer.