# Corepressors in regulatory T cell development and function

> **NIH NIH F31** · UNIVERSITY OF MINNESOTA · 2021 · $40,466

## Abstract

PROJECT ABSTRACT
Regulatory T cells (Tregs) are critical in dampening the immune response following an infection and
suppressing autoreactive cells. Defects in Tregs contribute to disease pathogenesis in some autoimmune
conditions. While much is known about the roles of individual transcription factors in regulating Treg biology,
the involvement of these transcription factors in the epigenetic regulation of Tregs remains largely unexplored.
Treg-promoting transcription factors include FOXP3, STAT5, and SMAD2/3-SMAD4. These transcription
factors promote Treg-specific gene expression and silence genes associated with other T helper subsets. The
precise mechanism through which they positively and negatively regulate gene transcription remains unclear.
Transcription factors can associate with corepressors, which then recruit histone deacetylases to the site of
DNA binding. The resulting histone deacetylation decreases gene transcription. FOXP3, STAT5, and SMAD
are all known to associate with corepressor proteins NCOR1 and NCOR2/SMRT. These interactions suggest a
role for NCOR1/2 in regulating Tregs. Preliminary data obtained from NCOR1/2-deficient mice demonstrate a
severe quantitative defect in all CD4 T cells, including Tregs. NCOR1/2-deficient mice also have impaired
thymic Treg development and reduced differentiation into Tregs from naïve CD4 T cells. The effects of
NCOR1/2 deletion on Tregs recapitulate the phenotype observed in STAT5-deficient mice. I hypothesize that
the association of Treg-promoting transcription factors and NCOR1/2 promote normal Treg
development and function through control of epigenetic modifications. My hypotheses will be tested by
pursuing the following aims: (1) identifying the contribution of NCOR1/2 to Treg differentiation and function and
(2) defining the contributions of transcription factor-NCOR1/2 complexes to the epigenetic landscape of Tregs.
Completion of these studies will reveal important information about the role of epigenetic modifications in Treg
differentiation and homeostasis. It will also provide insight into developing therapies to enhance Treg quantity
and function and restore immunological tolerance in autoimmune diseases.

## Key facts

- **NIH application ID:** 10315335
- **Project number:** 1F31AI157166-01A1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Natalie Anne David
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $40,466
- **Award type:** 1
- **Project period:** 2021-08-08 → 2024-08-07

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10315335

## Citation

> US National Institutes of Health, RePORTER application 10315335, Corepressors in regulatory T cell development and function (1F31AI157166-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10315335. Licensed CC0.

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