# Investigate the impact of physiological microbial exposure on regulatory T cell-mediated immune regulation

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $197,500

## Abstract

Rigorous biocontainment prevents laboratory mice from being infected with natural pathogens and allows
researchers to perform animal experiments in a reliable and reproducible manner. However, such specific
pathogen-free (SPF) mice do not necessily model immune responses that occur in nature, and this may
contribute to the often-reported disconnect between pre-clinical research and human clinical trials. Athough
many key advances in biomedical research have been made possible by the study of SPF mice, there is
now compelling evidence that microbial or viral experience can greatly impact immune pathophysiology. In
past two decades, regulatory T (Treg) cells have emerged as a dedicated immune population crucial for the
negative regulation of immune responses. Considering that Treg cell homeostasis and function can be
greatly influenced by unique signals present in different tissue environments, it is conceiable that the
microbial exposure outside the current laboratory setting could heavily impact Treg cells and their ability not
only to establish immunological tolerance against ‘‘self’’ or innocuous foreign antigens, but also to keep in
check effector immune responses to pathogens. To gain a better understanding of Treg cell-mediated
immune regulation in a more physiological setting, we have worked closely with the Animal Care Program at
UC San Diego to establish a new protocol to generate, maintain, and extensively characterize a stable
repository of physiological microbe-exposed environmentally conditioned (PC) animals. By taking this
approach, two well-establsihed mouse models that affords Treg cell isolation and Treg cell-specific ablation
will be first adapted to the “dirty” condition. Next, through performing extensive comparative immune
phenotype analysis and single-cell sequencing studies of Treg cells isolated from both lymphoid and
non-lymphoid tissues in SPF mice and PC mice, the impact of physiological microbial exposure on Treg cell
biology will be determined. Finally, we will examine the suppressor function of Treg cells from PC mice to
maintain immune homeostasis and to control ongoing inflammation in comparison with their SPF
counterparts. Together, our study will not only further extend our fundamental knowledge of Treg
cell-dependent immune regulation but also provide critical insights into the possibilities and limitations of
targeting Treg cells to treat a wide array of human immunological diseases.
.

## Key facts

- **NIH application ID:** 10876391
- **Project number:** 5R21AI178396-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Li-Fan Lu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $197,500
- **Award type:** 5
- **Project period:** 2023-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10876391

## Citation

> US National Institutes of Health, RePORTER application 10876391, Investigate the impact of physiological microbial exposure on regulatory T cell-mediated immune regulation (5R21AI178396-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10876391. Licensed CC0.

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