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

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $424,335

## 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 intestinal adaptive immune responses, including the homing of T and B cells to the intestine
and immunoglobulin A production. These vitamin A-dependent immune responses depend on specialized
intestinal myeloid cells that enzymatically convert the vitamin A derivative retinol to retinoic acid (RA). In the
previous project period we unraveled a molecular mechanism by which intestinal myeloid cells acquire retinol.
We discovered that serum amyloid A (SAA) proteins – microbiota-inducible epithelial cell proteins – are retinol
chaperones that deliver retinol to myeloid cells via the endocytic receptor LRP1 (low density lipoprotein-related
receptor 1). We found that this mechanism is essential for the development of intestinal adaptive immunity and
for immune protection against pathogenic bacterial infection. This R01 renewal application will build on these
findings to further define the biochemical, cell biological, and microbiological mechanisms that regulate retinol
delivery to intestinal myeloid cells and thus promote vitamin A-dependent immunity. In Aim 1, we will determine
how SAA-retinol complexes are assembled and secreted from intestinal epithelial cells. In Aim 2, we will identify
the SAA-LRP1 interface and determine its importance for myeloid cell retinol uptake and vitamin A-dependent
immunity. In Aim 3, we will define the role of the intestinal microbiota in regulating myeloid cell retinol acquisition
and vitamin A-dependent immunity. These studies will provide mechanistic insight into how vitamin A is mobilized
to intestinal immune cells and advance our understanding of how the gut microbiota regulates the intestinal
adaptive immune system. Our findings will help identify new strategies for inhibiting or enhancing vitamin A
mobilization to the intestinal immune system in order to treat infection and inflammation.

## Key facts

- **NIH application ID:** 10912755
- **Project number:** 5R01DK070855-20
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** LORA V HOOPER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $424,335
- **Award type:** 5
- **Project period:** 2005-06-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10912755

## Citation

> US National Institutes of Health, RePORTER application 10912755, Microbial Regulation of Retinol Transport and its Role in Intestinal Immunity (5R01DK070855-20). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10912755. Licensed CC0.

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