# STING signaling in T cells regulation of intestinal homeostasis and inflammatory  bowel diseases

> **NIH NIH R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2020 · $503,932

## Abstract

ABSTRACT
STING (stimulator of interferon genes), a cytoplasmic sensor for cyclic dinucleotides (CDNs), plays a crucial role
as an adaptor molecule for a number of intracellular DNA receptors. The upstream DNA sensors that signal
through STING include cyclic GMP-AMP synthase (cGAS), IFN-inducible proteins, and DExD/H-box helicase
family proteins, highlighting an important function for STING in controlling multiple DNA recognition pathways.
STING has been crucial in host defense against viral, bacterial, and eukaryotic pathogens, and also to the
development of autoimmune disease. Abnormalities in this defense mechanism can underpin a spectrum of
conditions, including cancer and autoinflammatory diseases. STING is thus a highly promising drug target.
Recent studies have underscored the role of STING in regulating intestinal inflammation and tumorigenesis. As
high levels of microbiota-derived DNA and CDNs are present in the gut, these stimuli could contribute to local
activation of STING at steady state. Sting-/- mice have been reported to develop more severe colitis upon acute
inflammatory insult. Our preliminary data demonstrated that T cells expressed STING at levels higher than that
in dendritic cells (DCs). Furthermore, activation of STING signaling promoted T cell production of IL-10 and IL-
22 but inhibited IL-17 production, indicating that STING may potentially regulate intestinal homeostasis and colitis
development by promoting anti-inflammatory IL-10/IL-22 and inhibiting proinflammatory cytokine production by
T cells. In this application, we will test whether STING promotes T cell production of IL-10 and IL-22 by inducing
IRF4 and AHR expression mediated by the production of type I IFNs by both T cells and dendritic cells, which
would lead to the preservation of intestinal immune homeostasis and inhibition of IBD. Furthermore, we will test
whether STING agonists can prevent and treat colitis.

## Key facts

- **NIH application ID:** 10071757
- **Project number:** 1R01DK124132-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Yingzi Cong
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $503,932
- **Award type:** 1
- **Project period:** 2020-07-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10071757

## Citation

> US National Institutes of Health, RePORTER application 10071757, STING signaling in T cells regulation of intestinal homeostasis and inflammatory  bowel diseases (1R01DK124132-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10071757. Licensed CC0.

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