# Interferons in Treg development and function

> **NIH NIH F31** · UNIVERSITY OF MINNESOTA · 2021 · $44,406

## Abstract

ABSTRACT
Thymically-derived regulatory T-cells (Tregs) are critical for controlling immune responses and preventing
autoimmunity. In the setting of viral infection, Tregs are important modulators of anti-viral immune responses
and help to prevent excessive tissue damage. The subset of Tregs responsible for responding to viral
infections and what types of antigens they are recognizing is not well understood. This proposal aims to
address this gap in knowledge. In single-cell RNA sequencing experiments of thymic Tregs and Treg
progenitors, I have observed a unique cell subset that express a strong interferon stimulated gene (ISG)
signature. I hypothesize that thymic Tregs receiving IFN stimulation are enriched for expression of TCRs that
recognize ISG-derived antigens presented by thymic APCs. Furthermore, I propose that these Tregs are
important responders to IFN-induced inflammation in the periphery including viral infection and help to limit
immune responses in these settings. I will test this hypothesis in two specific aims: In aim 1 I will use a novel
mouse model in which Tregs expressing the ISG-signature will be deleted following administration of diphtheria
toxin. Treg responses to influenza virus infection will be evaluated in this context to determine the importance
of these ISG-signature Tregs in responding to IFN-induced inflammation. In aim 2 I will use mice with
conditional knockout of Stat1 in thymic epithelial cells and dendritic cells to determine how Treg responses to
IFN-induced inflammation are altered when they develop in the absence of interaction with ISG antigens in the
thymus. Additionally, I will use spatial transcriptomic technology to visualize the thymic niche expressing IFNs
and ISGs, as well as the progenitor and mature ISG-signature Treg subsets.

## Key facts

- **NIH application ID:** 10234449
- **Project number:** 1F31AI154706-01A1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Lucy Sjaastad
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $44,406
- **Award type:** 1
- **Project period:** 2021-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10234449

## Citation

> US National Institutes of Health, RePORTER application 10234449, Interferons in Treg development and function (1F31AI154706-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10234449. Licensed CC0.

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