# Translational Regulation of T Regulatory Cells

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $723,477

## Abstract

PROJECT SUMMARY
Regulatory T cells (Tregs) are lymphocytes that constitute ~5% of CD4+ T cells which suppress the activation of
other immune cells. While there is a detailed transcriptional understanding of T cell development, including the
development of Tregs, historically there has been little understanding of the translational regulation of T cell
lineage commitment and function, including that of Tregs. We recently demonstrated that Treg development
involves a novel, specialized translation mechanism carried out by a poorly investigated translation factor
complex we termed DAP5/eIF3d, that is independent of canonical mTORC1 and eIF4E. DAP5/eIF3d is an
alternate mechanism of cap-dependent mRNA translation which we discovered and recently showed is unique
to Tregs among T cell types. This work lays a foundation for studies in this renewal application to understand
how the novel DAP5/eIF3d mechanism controls Treg cell plasticity, function and stability, and integrates other
molecular regulatory events in Treg development and function.
 We hypothesize that DAP5/eIF3d specialized mRNA translation is required for the differentiation of Tregs
(tTregs, pTregs, iTregs) and involves specific m6A modification of Treg mRNAs. Studies are described in this
application to now more fully characterize how DAP5/eIF3d specialized mRNA translation regulates Treg lineage
commitment, the molecular mechanisms by which Treg mRNAs are selectively translated, including by an m6A-
DAP5/eIF3d mechanism. There is currently little understanding of translational regulation of Tregs, and no
understanding of the translational regulation of exTregs, which will also be investigated.
 Four Specific Aims have been developed to investigate the role of canonical eIF4E/mTORC1 versus
specialized DAP5/eIF3d mediated mRNA translation in Treg translational control of lineage determination,
stability and function. Aim 1. Characterize DAP5 dependent mRNA translation in development and stability of
tTreg and pTreg cell subtypes in the mouse. Aim 2. Investigate the role of DAP5 expression level in generation
of exTregs and Treg-exTreg phenotypic plasticity. Aim 3. Characterize mRNA translational reprogramming in
Treg subtype lineage commitment and function. Aim 4. Determine the role of m6A with DAP5 in selective
translation of Treg cell lineage determining mRNAs, suppression function and Treg cell stability.

## Key facts

- **NIH application ID:** 10901514
- **Project number:** 2R01AI137067-06A1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Robert Jay Schneider
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $723,477
- **Award type:** 2
- **Project period:** 2024-03-01 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10901514

## Citation

> US National Institutes of Health, RePORTER application 10901514, Translational Regulation of T Regulatory Cells (2R01AI137067-06A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10901514. Licensed CC0.

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