# Treg aging and its implication in viral infection

> **NIH NIH R56** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $314,756

## Abstract

Project Summary:
 Age-related health issues have become a major and increasing health challenge worldwide. The
deterioration of the immune function during aging, hallmarked by the aberrant accumulation of effector-memory
T cells and elevated inflammatory SASP (senescence-associated secretory phenotype) has long been
recognized to prominently contribute to aging and related diseases, esp. during the outbreak of emerging
pathogens, such as COVID-19 pandemic. It is vital to reveal the cellular and molecular mechanisms underlying
immunological aging. The proper function of immune system can only be ensured by well-balanced immune
activation (mediated by conventional T cells) and immune suppression (mediated by Treg cells). However, the
function and regulation of age Tregs and the implication in infection remains a knowledge gap to be filled.
 Our preliminary study revealed that (1) Aged Tregs severely senesced and reduced function in vitro
and in vivo during aging (2) Reactive-oxygen-species (ROS) was upregulated in aged Treg. (3) Interfering with
ROS pathway reinvigorated the proliferation and function of aged Tregs. Because Tregs play important and
multifaceted roles in controlling inflammation, infection, and tissue repair, these preliminary results provide the
scientific premise for the central hypothesis that declined proliferation and function of aged Tregs negatively
impacts the outcome of viral infection in the elderly, and that uncovering the cellular and molecular
mechanisms underlying Treg aging will aid the efforts to reinvigorate aged Tregs to help improve elderly's
ability to fight emerging pathogens. To test this hypothesis, we propose to reach the following three specific
research aims. AIM 1: Investigate the cellular heterogeneity and dynamics of Tregs in aged mice during
infection. AIM 2: Understand how ROS accumulation is controlled in aged Tregs. AIM 3: Address if the
outcome of infection can be improved through reinvigorating the function of aged Tregs.
 There is a great and yet unmet need in the understanding of the cellular and molecular mechanisms
underlying immunological aging and infection. This study aims to reveal previous unappreciated Treg-
dependent cellular and molecular mechanisms underlying weaken ability to fight infection by the elderly. The
success of this study will gain critical understanding of immune response during aging, advance the fields of
geriatrics, provide mechanistic insights in age-related syndromes, and uncover new perspectives on how to
mitigate age-related morbidity to improve the health of the aging population.

## Key facts

- **NIH application ID:** 10490482
- **Project number:** 1R56AG071256-01A1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Yisong Wan
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $314,756
- **Award type:** 1
- **Project period:** 2021-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10490482

## Citation

> US National Institutes of Health, RePORTER application 10490482, Treg aging and its implication in viral infection (1R56AG071256-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10490482. Licensed CC0.

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