# Development of Immune Tolerance

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2022 · $460,057

## Abstract

PROJECT SUMMARY
Programming of self-antigen specific CD4+ Tregs in the thymus is essential for suppression of aberrant
immune responses and prevention of autoimmunity. Tregs also control inflammation during viral infection and
following pathogen clearance. This is particularly relevant for some types of viral infections such as the 1918
influenza pandemic strain, and more recently, specific strains of coronaviruses, where the immune response
itself can be pathogenic. In addition to viral infections, high levels of type I IFN are a defining feature of some
autoimmune diseases, such as SLE or Sjögren’s syndrome; Tregs reduce the symptoms of such autoimmune
diseases as well. However, we know relatively little about the Tregs involved in either of the above processes.
For example, what types of Tregs are involved in these responses? Do Tregs that dampen anti-viral immune
responses or suppress SLE-like disease develop in the thymus? If so, what is the thymic niche that controls
differentiation of this Treg subset? What APCs/stromal cells are required for differentiation of this Treg subset?
What specific functional roles does this Treg subset play during viral infections or SLE? Our preliminary data
demonstrate that a unique subset of Tregs develops in the thymus characterized by a strong
interferon-stimulated gene-signature (ISG-Tregs). We propose that this ISG-Treg subset plays a key
role in governing antiviral immune responses and suppressing immune responses to autoimmune
diseases characterized by high levels of IFN. We will explore this hypothesis in two specific aims. In aim 1,
we will determine how IFN signaling in the thymus affects thymic selection and the development of ISG-Tregs.
In aim 2, we will determine the functions of ISG-Tregs in response to viral infections and systemic lupus
erythematosis. Successful completion of these aims will allow us to identify the mechanism by which ISG-
Tregs arise in the thymus, and determine the role of ISG-Tregs in immune responses to viruses, and in
autoimmune diseases associated with high levels of IFN, such as SLE or Sjögren’s syndrome.

## Key facts

- **NIH application ID:** 10338131
- **Project number:** 5R01AI124512-07
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Michael Archibald Farrar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $460,057
- **Award type:** 5
- **Project period:** 2016-03-15 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10338131

## Citation

> US National Institutes of Health, RePORTER application 10338131, Development of Immune Tolerance (5R01AI124512-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10338131. Licensed CC0.

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