# Investigating the Role of IL-23R in Mucosal Regulatory T Cells

> **NIH NIH R03** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $129,750

## Abstract

Project Summary
Dysregulated immune responses to luminal bacteria in the intestine are largely responsible for the chronic
nature of inflammatory bowel disease (IBD). Attenuating the inflammatory response via immunomodulators
and/or biologics represent the majority of therapeutic strategies to induce remission. However, many patients
either do not respond and those that initially do often stop responding. Restoring immune tolerance by
increasing regulatory T cell (Treg) numbers or improving Treg function may be a viable strategy to achieve
long-term remission. The PI’s K01 award has focused on strategies to expand Tregs in vivo to prevent
experimental colitis in humanized mice. In the course of these studies, the cytokine interleukin-23 (IL-23) was
upregulated in murine and human antigen presenting cells. Consistent with a role for IL-23 in IBD, variants in
IL23R have been linked to IBD susceptibility. Furthermore, a recent phase 3 clinical trial in patients with
Crohn’s disease targeted the p40 subunit of IL-23 (also shared with IL-12) and reported significant
improvement in both induction and maintenance of clinical response and remission over placebo. Although
macrophage and dendritic cells in the intestine are the source of IL-23, expression of IL-23R is generally
restricted to lymphocytes and type 3 innate lymphoid cells (ILC3s). In this proposal, we will determine the role
of IL-23R in Tregs in intestinal immune homeostasis and during inflammation using mice harboring floxed Il23r
alleles combined with a Cre recombinase driven by the endogenous Foxp3 promotor. In Aim 1, we will
determine the role of IL-23R in FOXP3+ Tregs during inflammation and inflammation-associated
carcinogenesis. In Aim 2, we will define the transcriptional, metabolic, and signaling networks/pathways
modulated by IL-23R signaling in intestinal FOXP3+ cells. Overall, these studies explore in detail how IL-23R
differentially impacts mucosal immunity and it’s role during inflammation that will inform future therapeutic
strategies for IBD and colon cancer. This proposal will further advance the independent studies of the PI and
facilitate his transition as a successful investigator and leader in the field of mucosal immunology and will
provide sufficient published and preliminary data to facilitate a highly competitive application for a R01 grant
application as an early-stage investigator.

## Key facts

- **NIH application ID:** 10057505
- **Project number:** 1R03DK123489-01A1
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Jeremy Allen Goettel
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $129,750
- **Award type:** 1
- **Project period:** 2020-07-10 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10057505

## Citation

> US National Institutes of Health, RePORTER application 10057505, Investigating the Role of IL-23R in Mucosal Regulatory T Cells (1R03DK123489-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10057505. Licensed CC0.

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