# Adrenergic control of circadian rhythms in CD8 T cells responding to influenza

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $617,814

## Abstract

PROJECT SUMMARY
This application seeks to understand how circadian rhythms control T cell immunity to influenza infection
through signals delivered by the sympathetic nervous system. Circadian rhythms are biological clocks that are
entrained by light/dark cycles, and in mammals, those rhythms are synchronized systemically throughout the
body via signals delivered by sympathetic and parasympathetic neurons. Our recent studies uncovered an
unexpected role for the β2-adrenergic receptor in cytolytic responses of CD8+ T cells to a virus infection.
Further, we found that selective deletion of the Adrb2 on CD8+ T cells profoundly disrupted circadian gene
expression and oscillation frequencies as a function of light/dark entrainment. This proposal will test the
hypothesis that the signaling through the ADRB2 in CD8+ T cells regulates circadian rhythm genes, and that
those genes are required for orchestrated T cell responses to influenza infection. Aim 1 will distinguish the roles
of the Adrb2 and downstream core clock in CD8-mediated lung inflammation during influenza infection. Aim 2
will determine how jet-lag impacts CD8+ T cell responses to influenza. This proposal tests a very straight-
forward hypothesis, which if supported, will be the first to connect a circadian rhythm entrainment receptor to
downstream T cells responses to influenza. The outcomes of this research will significantly advance our
understanding of environmental pathways that regulate immune responses to influenza and improve mouse
models of viral pathogenesis and vaccine design.

## Key facts

- **NIH application ID:** 10876387
- **Project number:** 5R01AI175217-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** John David FARRAR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $617,814
- **Award type:** 5
- **Project period:** 2023-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10876387

## Citation

> US National Institutes of Health, RePORTER application 10876387, Adrenergic control of circadian rhythms in CD8 T cells responding to influenza (5R01AI175217-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10876387. Licensed CC0.

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