# Role of RORgt+ (note: g: is gamma symbol) lymphocytes in Gut Tissue Homeostasis

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2022 · $560,517

## Abstract

Project Summary/Abstract:
ILC3s, gdT17 and Th17 cells share common features, e.g., expressing the master transcription factor RORgt
and the effector cytokines IL-17A, IL-17F and IL-22, and perform distinct immune functions under different
environment context. Our preliminary data suggest that RORgt+ cell-intrinsic deletion of Tfam in Tfamfl/flRorc-
cre mice affected RORgt+ gdT17 cells and ILC3s in vivo maintenance and led to small intestinal tissue
remodeling via a tuft cell–ILC2 circuit. An emerging concept of mitochondrial control of immunity beyond ATP
generation has recently been proposed. Based on the premise and our preliminary data, we hypothesize that
that Tfam-mediated mitochondrial respiration in gdT17 cells and ILC3s is pivotal for gdT17/ILC3 cell
homeostasis and regulation of small intestine tissue remodeling/metabolic changes and
immunity/inflammation. Specifically, we will investigate 1) the role of Tfam in gdT17 and ILC3 lymphocyte
maintenance, 2) the role of Tfam in gdT17 cells and/or ILC3s in regulating tuft cell-ILC2 circuit and small
intestine tissue remodeling, and 3) the role of Tfam in gdT17 cells and/or ILC3s in regulation of microbiome and
small intestinal immunity and inflammation. These experiments will offer an opportunity to elucidate Tfam-
mediated mitochondrial respiration in RORgt+ lymphocytes in the small intestine under the steady state and
during infection/immunity. Our study will provide novel cellular and molecular insights into the maintenance and
function of gdT17 cells and ILC3s regulated by Tfam. Understanding the mechanisms underlying the
requirement of Tfam for RORgt+ cells in regulation of small intestine tissue remodeling and immunity may
represent a new paradigm for human disease treatment and/or prevention.

## Key facts

- **NIH application ID:** 10456906
- **Project number:** 5R01AI157109-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Liang Zhou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $560,517
- **Award type:** 5
- **Project period:** 2021-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10456906

## Citation

> US National Institutes of Health, RePORTER application 10456906, Role of RORgt+ (note: g: is gamma symbol) lymphocytes in Gut Tissue Homeostasis (5R01AI157109-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10456906. Licensed CC0.

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