# The role of miR-142 in regulatory T cell Development and function

> **NIH NIH R01** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2020 · $440,000

## Abstract

Project Summary
Regulatory T (Treg) cells are vital for maintaining immunological self-tolerance and restraining overreactive
immune responses against infection. Aberrant Treg cell activity is associated with autoimmune diseases and
unproductive immune responses against tumors. An insufficient understanding of the molecular mechanisms
that govern Treg cell biology is one of the critical barriers hampering development of effective Treg cell-based
therapies for autoimmunity and cancer. Post-transcriptional control of gene expression by microRNAs (miRNAs)
has recently emerged as an essential genetic element for Treg cell differentiation and function. Thus, the objective
of this proposal is to gain better understanding of how individual miRNAs control central aspects of Treg cell
biology. Closing of this knowledge gap may allow us to develop novel, targeted immunotherapies for treatment
of Treg cell-mediated diseases. The focus of this proposal is to elucidate the function of miR-142 in Treg cells. Our
results using genetic knockout mouse models indicate that miR-142 is an indispensable regulator of Treg cell-
mediated immunosuppression. We uncovered two distinct roles for miR-142 in Treg cells: it promotes thymic Treg
cell differentiation and positively regulates mature Treg cell homeostasis and suppressive activity. Moreover, we
mechanistically linked the impaired function of mature miR-142-deficient Treg cells with excessive IFNg production
and signaling, and identified several IFNg-associated genes as direct molecular targets of miR-142. Thus, our
overall hypothesis is that miR-142 plays a crucial role in thymic Treg cell development and controls Treg cell
abundance and functional activity. Furthermore, we posit that miR-142 regulates mature Treg cell homeostasis
and suppressive function by attenuating production of and responsiveness to IFNg. We will test our central
hypothesis with three specific aims. In Aim 1, we will investigate the role of miR-142 in thymic Treg cell
development and define its mode of action. In Aim 2, we will determine the impact of inducible miR-142 depletion
on Treg cell homeostasis and suppressive function in the context of antitumor immune response. Finally, in Aim
3, we will identify the molecular mechanism of miR-142-mediated control of Treg cell activity. To that end, we will
determine how dysregulated IFNg signaling impacts the immunosuppressive activity and homeostasis of
miR-142-deficient Treg cells. The proposed research is significant because it is expected to advance our
understanding of miRNA-mediated mechanisms underlying the control of Treg cell function and immune
tolerance. Additionally, this study may potentially lay a foundation for developing a novel miR-142-based
therapeutic strategy for modulating Treg cell activity in cancer immunotherapy and autoimmune disease settings.

## Key facts

- **NIH application ID:** 10121945
- **Project number:** 1R01AI146313-01A1
- **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
- **Principal Investigator:** Mark P Boldin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $440,000
- **Award type:** 1
- **Project period:** 2020-09-17 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10121945

## Citation

> US National Institutes of Health, RePORTER application 10121945, The role of miR-142 in regulatory T cell Development and function (1R01AI146313-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10121945. Licensed CC0.

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