# Lipid-dependent regulation of human Th17 cell function

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 2020 · $447,958

## Abstract

Abstract
Th17 cells are an Interleukin-17-producing subset of CD4+ T effector cells that are centrally
implicated in many human inflammatory and autoimmune diseases, from inflammatory bowel
disease to multiple sclerosis. The retinoid orphan receptor gamma t (RORγt), a nuclear hormone
receptor, programs Th17 cell development and function. With the ultimate goal of modulating
inflammatory T cells in disease settings, we undertook chemical and genetic screening to
identify RORγt target genes that drive human Th17 cell function. Intriguingly, our results
implicated a group of genes in a novel pathway that would link lipid metabolism, RORγt activity
and Th17 cell functions. We will thus test the hypothesis that Th17 cell function is controlled in
large part, by RORγt target genes, via lipid droplets (LDs) (cellular organelles associated with
lipid metabolism). We will take the following approaches: First, we will determine if LD- related
genes – specifically, HILPDA and BNIP3 – are necessary, sufficient and specific regulators of
human Th17 cell functions. Second, we will elucidate the molecular mechanisms by which LDs
modulate Th17 cell differentiation. Third, using autoimmune disease models in mice, we will
determine the physiological significance of LDs in inflammation and autoimmune pathologies.
Our results may shed a light on novel lipid-regulatory mechanisms that control Th17 cell
responses in inflammatory diseases.

## Key facts

- **NIH application ID:** 9964794
- **Project number:** 5R01DK106351-06
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Jun R. Huh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $447,958
- **Award type:** 5
- **Project period:** 2016-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9964794

## Citation

> US National Institutes of Health, RePORTER application 9964794, Lipid-dependent regulation of human Th17 cell function (5R01DK106351-06). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9964794. Licensed CC0.

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