# Foxp transcription factors in regulatory T cells

> **NIH VA I01** · VETERANS ADMIN PALO ALTO HEALTH CARE SYS · 2021 · —

## Abstract

Regulatory T cells (Tregs) are critical for actively maintaining immune tolerance. The Foxp family of
transcription factors is composed of four members; Foxp1, Foxp3 and Foxp4 are expressed in lymphocytes.
Foxp family members bind DNA as homo- and hetero-dimers to regulate gene expression. Regulatory T cells
are CD4+ T cells that express Foxp3. We have generated mice in which both Foxp1 and Foxp4 are deleted in
either all T lymphocytes or in Tregs, leaving Foxp3 the only potentially expressed family member in this T cell
subset. Our preliminary data demonstrate that combined loss of Foxp1 and Foxp4 in all T lymphocytes based
on CD4 Cre-mediated deletion substantially alters the development of Tregs in the thymus, reduces peripheral
Treg cellularity, and alters suppressive function. When loss of Foxp1 and Foxp4 is limited to the Foxp3+ Treg
population, there is a dramatic phenotype characterized by lymphocyte activation/expansion, autoantibody
production, and early lethality. The overall goal of this proposal is to understand how Foxp1 and Foxp4 alter
the development, homeostasis and function of Foxp3+ Tregs. To address this question we propose to
generate and use novel mouse strains in which Foxp1 and Foxp4 are deleted at different stages of Treg
development. We will use high throughput sequencing technology to investigate gene regulation by Foxp1
and/or Foxp4. We will test Tregs deficient in Foxp1 and Foxp4 in relevant models of autoimmunity and
transplantation. Understanding these fundamental aspects of Treg generation, homeostasis and function are
critical to translational strategies of Treg augmentation being developed for use in autoimmune disease and
solid-organ transplantation.

## Key facts

- **NIH application ID:** 10125490
- **Project number:** 1I01BX005142-01A1
- **Recipient organization:** VETERANS ADMIN PALO ALTO HEALTH CARE SYS
- **Principal Investigator:** JONATHAN S MALTZMAN
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2021-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10125490

## Citation

> US National Institutes of Health, RePORTER application 10125490, Foxp transcription factors in regulatory T cells (1I01BX005142-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10125490. Licensed CC0.

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