# LncRNA regulation of Type I IFN signaling in intestinal epithelium

> **NIH NIH R21** · RUSH UNIVERSITY MEDICAL CENTER · 2021 · $235,500

## Abstract

Summary
Epithelial cells along the mucosal surface provide the front line of host defense against pathogen infection in
the gastrointestinal (GI) tract. These epithelial cells represent an integral component of a highly regulated
communication network that can transmit essential signals to cells in the underlying GI mucosa that, in turn,
serve as targets of mucosal immune mediators. How intestinal epithelial cells orchestrate GI mucosal
defense is still not fully understood. LncRNAs are recently identified long non-coding transcripts that can
regulate gene transcription through their interactions with other effect molecules. We have recently identified
a panel of lncRNAs that are upregulated in GI epithelial cells following microbial challenge. Specific lncRNAs
display a significant suppressive effect on Type I interferon (IFN)-controlled gene transcription in GI epithelial
cells. Interestingly, induction of some lncRNAs is controlled by Type I IFN signaling. Given the emerging
significance of lncRNAs in regulation of both innate and adaptive immune responses, coupled with the key
role of Type I IFN signaling in regulating GI homeostasis, we speculate that lncRNAs may be important
regulators in GI physiology and pathophysiology. In this study, we hypothesize that lncRNAs provide
negative feedback regulation of Type I IFN signaling through suppression of Type I IFN-controlled gene
transcription, consequently contributing to fine-tuning of epithelial cell innate defense against microbial
infection. We will use in vitro, ex vivo and in vivo infection models and complementary biochemical,
molecular, and morphologic approaches to elucidate the molecular mechanisms by which lncRNAs modulate
Type I IFN-mediated gene transcription in GI epithelial cells (Aim 1) and determine the role of lncRNA-
mediated feedback regulation of Type I IFN-mediated gene transcription in GI epithelial innate defense (Aim
2). Therefore, this application will explore a novel mechanism for lncRNAs in regulating GI mucosal innate
immunity. Elucidating the regulation of key signal pathways in GI epithelial cells by lncRNAs may reveal new
insights into the molecular immunology and immunopathology of the GI tract.

## Key facts

- **NIH application ID:** 10331247
- **Project number:** 7R21AI156370-02
- **Recipient organization:** RUSH UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Xian-Ming Chen
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $235,500
- **Award type:** 7
- **Project period:** 2020-12-23 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10331247

## Citation

> US National Institutes of Health, RePORTER application 10331247, LncRNA regulation of Type I IFN signaling in intestinal epithelium (7R21AI156370-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10331247. Licensed CC0.

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