# Microbial Regulation of Retinol Transport and its Role in Intestinal Immunity

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2022 · $364,500

## Abstract

Project Summary
The intestinal epithelium regulates the development of adaptive immunity to gut microorganisms, yet little is
known about the underlying mechanisms. Filling this knowledge gap is crucial, as many human intestinal
diseases arise from dysregulated intestinal immunity. Dietary vitamin A absorbed by the intestinal epithelium is
essential for key adaptive immune responses to the microbiota. These include the homing of CD4+ T cells to
the intestine and the development of B cells that produce immunoglobulin A. These responses depend on
specialized intestinal dendritic cells (DCs) that enzymatically convert the vitamin A derivative retinol to retinoic
acid (RA). A major unanswered question is how RA-producing DCs acquire their retinol. Retinol's lipid-like
chemical nature necessitates its transport by proteins that protect the retinol from the aqueous environment.
However, the protein(s) that mobilize retinol from the intestinal epithelium to DCs as substrate for RA
production remain unknown. We have gained insight into this question by studying serum amyloid A (SAA)
proteins, which are produced by the intestinal epithelium in response to the microbiota. This R01 renewal
application will explore the hypothesis that serum amyloid A (SAA) proteins mobilize retinol to RA-producing
DCs and thus shape intestinal adaptive immunity. In the previous project period, we discovered that SAAs are
retinol-binding proteins that circulate with bound retinol during acute systemic infection. Further preliminary
findings indicate that intestinal SAAs promote retinol acquisition by RA-producing DCs. We propose to build on
these findings during the next project period to gain a deeper mechanistic understanding of how SAAs shape
intestinal DC function and the development of intestinal adaptive immunity. In Aim 1, we will delineate the role
of SAAs in retinol acquisition and retinoic acid production by intestinal dendritic cells. In Aim 2, we will identify
the cellular receptor for retinol-bound SAAs. In Aim 3, we will determine the physiological relevance of SAAs
for the development of vitamin A-dependent adaptive immunity in the intestine. These studies will provide
mechanistic insight into how vitamin A is mobilized to intestinal immune cells and advance our understanding
of how microbiota-epithelial interactions shape adaptive immunity. Understanding how the microbiota controls
vitamin A-dependent immunity will promote the design of new therapeutics for inflammatory disorders and
vaccines against infections.

## Key facts

- **NIH application ID:** 10403962
- **Project number:** 5R01DK070855-18
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** LORA V HOOPER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $364,500
- **Award type:** 5
- **Project period:** 2005-06-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10403962

## Citation

> US National Institutes of Health, RePORTER application 10403962, Microbial Regulation of Retinol Transport and its Role in Intestinal Immunity (5R01DK070855-18). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10403962. Licensed CC0.

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