# Regulatory T cells impose specific translatome changes in effector CD4 T cells

> **NIH NIH F32** · UNIVERSITY OF WASHINGTON · 2020 · $28,938

## Abstract

Project Summary/Abstract
Regulatory T cells (Treg) are a distinct subset of immune cells that play a critical role in properly maintaining
immune homeostasis. Indeed, changes in Treg homeostasis or function is highly implicated in a variety of
autoimmune diseases settings as well as in cancer, suggesting clinical importance of understanding Treg
biology. Despite decades of research on Tregs, the molecular basis of how Tregs suppress unwanted immune
responses are unclear. The hurdle mainly comes from ‘too many’ mechanisms proposed as to how Tregs
function. Here, we propose a new paradigm for the function of Tregs with the central hypothesis that Tregs
impose a ‘core’ suppressive program in target effector CD4 T cells (Teff) at the level of ‘translation,’ the
process where proteins are generated from the genetic information encoded in the format of RNA. Although
proteins are the biomolecules that confer most biological function, it is surprising that the steady-state
abundance of mRNA known as the transcriptome is usually the end-point analysis chosen to explain
mechanisms of immune responses. We believe this gap comes from the lack of precise tools to interrogate the
translatome (all the mRNA transcripts that are translated in a given moment) in primary immune cells. We
repurposed the RiboTag genetic tool that introduces an epitope-tag in a core ribosomal protein to study the
translatome of primary immune cells by translating ribosome affinity purification (TRAP). Using this tool, we
propose to follow up on our preliminary observation that indeed Tregs are necessary and sufficient to regulate
the overall protein synthetic output in Teff cells both in vitro and in vivo. In Aim1, we will interrogate the
genome-wide changes in ribosome-bound mRNA transcripts during Treg encounter. We will then characterize
cis-regulatory elements (sequence within the mRNA molecule) in the specific mRNA transcripts using
bioinformatics analysis to understand the mechanism of such specificity. In Aim2, we will explore the
hypothesis that trans-acting protein factors associated with the ribosome (riboproteome) itself is under dynamic
regulation during Treg encounter. Using the same genetic tool that allows direct ribosome immunoprecipitation,
we will interrogate the entire proteome of such bound factors using mass spectrometry analysis. Delineation of
the logic behind how specific mRNAs are chosen in time and space to become functional protein molecules
may revolutionize the way we view gene expression control in immunity.

## Key facts

- **NIH application ID:** 9908473
- **Project number:** 1F32AI145283-01A1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Lomon So
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $28,938
- **Award type:** 1
- **Project period:** 2020-02-03 → 2020-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9908473

## Citation

> US National Institutes of Health, RePORTER application 9908473, Regulatory T cells impose specific translatome changes in effector CD4 T cells (1F32AI145283-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9908473. Licensed CC0.

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