# Investigating the local and systemic coordination of antiviral immunity by tissue-resident memory CD8 T cells in the skin

> **NIH NIH F30** · UNIVERSITY OF MINNESOTA · 2024 · $53,974

## Abstract

Project Summary/Abstract
Cutaneous viral infections, including vector-borne viruses, cause significant morbidity and mortality.
Vector-borne viruses are transmitted first to the skin through mosquito bites, then disseminate, causing a broad
spectrum of frequently devastating disease. Yet, strategies to thwart cutaneous viruses remain elusive.
Resident memory T cells (TRM) represent a promising target due to their potent effector functions and
localization at barrier tissues including the skin. In contrast to recirculating memory T cells, TRM stably occupy
nonlymphoid tissues (NLT) where they rapidly detect pathogen reinfection and initiate protective anamnestic
immune responses. In fact, skin TRM can provide complete protection against cutaneous challenge through
direct killing of infected cells and innate-like effector functions that establish an antiviral state. Extensive
preliminary data supports the broad range of TRM functions that can be leveraged therapeutically. It is unknown,
however, if skin TRM can be directed to limit viral spread in acute infection after targeted immunization. By
focusing on antiviral CD8 TRM populations in the skin, this proposal will identify TRM functions in host immunity
that may be harnessed against skin-borne infectious diseases. Building on preliminary data, Aim 1 will
determine whether CD8 TRM reactivation orchestrates immune cells in the skin. Aim 2 will determine the extent
to which skin TRM influence distal immunity. TRM must function from a fixed location, yet it is unclear if they are
to serve as a local alarm or one that is amplified to enhance immunity at other sites. Observations that local
inflammation has far-reaching effects on other tissues, creating a cascade of responses that heighten immunity
at an organismal level lend credence to the idea TRM provoke systemic immune effects. By understanding how
we can utilize TRM through TCR-dependent processes, we may be able to wield this population in a more broad
manner. Given the many parallels between mouse and human TRM, findings in my studies using reductionist
mouse models may readily be applied to clinical therapeutics.

## Key facts

- **NIH application ID:** 10900160
- **Project number:** 1F30AI181450-01A1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Olivia C. Smith
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $53,974
- **Award type:** 1
- **Project period:** 2024-08-26 → 2027-08-25

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10900160

## Citation

> US National Institutes of Health, RePORTER application 10900160, Investigating the local and systemic coordination of antiviral immunity by tissue-resident memory CD8 T cells in the skin (1F30AI181450-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10900160. Licensed CC0.

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