# TCR signaling in thymic selection: Role of innate immune activation

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2024 · $626,274

## Abstract

Summary
The thymus plays a critical role in preventing autoimmunity by deleting or inducing a Treg cell
fate in thymocytes that react to self-antigens present in the thymus. But it is unclear how the
thymus achieves tolerance to transiently expressed self-antigens, like those expressed in
induced immune states such as inflammation, wound repair, and germinal center reactions. We
have recently discovered that the thymus constitutively produces type I and III interferons and
class switched activated B cells, beginning quite early in life. Our published and preliminary data
show that these cytokines activate antigen presenting cells in the thymus environment and
cause reproducible changes in the T cell repertoire selected, particularly the Treg cell repertoire.
Thus, we seek to test the hypothesis that T cells need to be highly tolerant of induced immune
states (inflammation, germinal centers) in order to function in those states without inducing
autoimmune pathology.
The proposed research will: 1) Test if thymic IFN provides T cell tolerance to interferon
stimulated self-antigens, 2) Determine why IFNI/III deficient mice have a major thymic selection
defect, and 3) Test if IFNIII-licensed B cells select Treg cells that regulate humoral immune
responses.
These aims will provide a mechanistic understanding of the source and consequences of innate
immune activation in the thymus. Understanding T cell tolerance to self-antigens in immune
activated states is important because many human autoimmune diseases are associated with
or follow infections.

## Key facts

- **NIH application ID:** 10980932
- **Project number:** 1R01AI179749-01A1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Kristin A. Hogquist
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $626,274
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10980932

## Citation

> US National Institutes of Health, RePORTER application 10980932, TCR signaling in thymic selection: Role of innate immune activation (1R01AI179749-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10980932. Licensed CC0.

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