# How Vitamin D Receptor Influences Intestinal Barriers

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2024 · $501,689

## Abstract

Salmonella enterica serotypes are invasive enteric pathogens spread through fecal contamination of food
and water sources. It represents a constant public health threat in the U.S. and around the world. Impaired
intestinal barriers are associated with bacterial infection. Vitamin D and its receptor (VDR) levels are inversely
related to chronic inflammation in infectious diseases. The objective of this application is to study VDR regulation
of intestinal tight junctions (TJs) in response to Salmonella infection. Our publications and preliminary data have
shown that: (1) lack of VDR makes the host susceptible to Salmonella invasion; (2) Salmonella targets TJ
proteins (e.g., ZO-1, Claudin) and facilitates pathogenic enteric bacterial invasion. (3) We have identified the
sequence of functional vitamin D response element in Claudin- 5 and 15, two novel target genes of VDR; (4)
impaired VDR leads to reduced expression of TJ proteins Claudin- 5 and 15, increased “leaky” protein Claudin
2, and increased permeability in infection; and (5) probiotics and their products enhance VDR function and inhibit
Salmonella infection. Thus, we hypothesize that: “intestinal epithelial VDR regulation of barrier function is
aberrant or lost in infectious states and restoring VDR function will attenuate severe infection and chronic
inflammation.” We have now developed state-of-the-art transgenic models and cutting-edge methods, e.g.,
integrated three-dimensional microscopy for a spatial junction protein atlas and single-cell spatial proteomics for
geographic profiling of the TJ protein expressions. Our research team includes experts in the following areas:
epithelial biology, animal models, bioengineering, and microbiology. Two Specific Aims have been designed:
 Aim 1. Determine the cellular and molecular mechanisms by which intestinal VDR regulates barrier
function that is essential for mucosal homeostasis. We will: A. Elucidate the mechanism for abnormal
epithelial TJs coregulated by Claudins and their interactions in the VDR-/- organoids in vitro. B. Study regional
and spatial Claudins, their interactions, and integrations with other barrier layers: microbiome and mucin. And C.
Determine the mechanism for abnormal epithelial TJs, including spatial and omics studies of TJs, in the intestine
of the VDRΔIEC and VDR overexpressed mice with or without infection. Aim 2. Investigate microbial
metabolites and TJs vs. VDR for therapeutic strategies in inflammation and infection. We will A. Evaluate
the roles and mechanisms of enhanced intestinal TJs vs. VDR expression by probiotic lactic acid bacterial
proteins and metabolites in infected mice. B. Engineer probiotic bacteria strains for better outcomes in treatment
of inflammation and infection. Our studies are innovative because they are focused on 1) understanding novel
regulatory roles of VDR in Claudins and their interactions in infection; 2) developing cutting edge technologies
and tools (organoids, transgenic mice, and sp...

## Key facts

- **NIH application ID:** 10801484
- **Project number:** 2R01DK114126-05A1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Jun Sun
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $501,689
- **Award type:** 2
- **Project period:** 2018-04-01 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10801484

## Citation

> US National Institutes of Health, RePORTER application 10801484, How Vitamin D Receptor Influences Intestinal Barriers (2R01DK114126-05A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10801484. Licensed CC0.

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