# Regulation of TH17 plasticity and stemness by mTORC1

> **NIH NIH R01** · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2020 · $448,750

## Abstract

Program Description/Abstract
Lineage commitment and maintenance are fundamental processes in a variety of biological systems. In the
immune system, dysregulated T cell responses are the cause of many allergic and inflammatory disorders.
TH17 cells play a key pathogenic role in Multiple sclerosis (MS) and its murine model, experimental
autoimmune encephalomyelitis (EAE). A unique feature of TH17 cells is their inherent plasticity that endows
mature effector TH17 cells with characteristics of other T cell subsets especially TH1 cells, but how this process
is controlled and its functional significance remain elusive. Coordination of T cell metabolic programs with cell
fate decisions is a fundamental process in adaptive immunity, but how metabolic pathways intersect with
immune signals in T cell fate decisions and autoimmune dysregulation is poorly defined. In particular, the
function of metabolic programs in effector T cell plasticity and pathogenicity remains essentially unexplored.
We hypothesize that the inherent heterogeneity of TH17 cells underlies their lineage plasticity; the balance between terminal differentiation and sustained stemness depends upon mTORC1 signaling and metabolic reprogramming, and contributes to autoimmune inflammation. Aim 1. Determine transcriptional mechanisms and developmental trajectory
underlying TH17 terminal differentiation and stemness. Aim 2. Establish the signaling and metabolic
mechanisms of mTORC1 in TH17 responses. Aim 3. Establish metabolic control and signaling circuits of TH17
plasticity. There has been little description of molecular pathways regulating TH17 lineage plasticity. We argue
that insight into metabolic control of TH17 plasticity could establish a new paradigm of T cell fate control
mechanisms, and manifest legitimate therapeutic opportunities for autoimmune diseases.

## Key facts

- **NIH application ID:** 9846189
- **Project number:** 5R01AI131703-03
- **Recipient organization:** ST. JUDE CHILDREN'S RESEARCH HOSPITAL
- **Principal Investigator:** Hongbo Chi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $448,750
- **Award type:** 5
- **Project period:** 2018-02-13 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9846189

## Citation

> US National Institutes of Health, RePORTER application 9846189, Regulation of TH17 plasticity and stemness by mTORC1 (5R01AI131703-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9846189. Licensed CC0.

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