# Targeting intestinal vitamin D receptor signaling to mitigate graft-versus-host disease

> **NIH NIH R21** · MEDICAL COLLEGE OF WISCONSIN · 2020 · $246,500

## Abstract

Abstract
Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic
stem cell transplantation (HSCT). It occurs because immunocompetent donor T cells in the allograft recognize
the genetically disparate host as foreign and attack the transplant recipient's tissues. While genetic
incompatibility between the donor and the recipient is the primary factor that determines the extent of the
alloimmune response, non-genetic factors can also influence the incidence and severity of GVHD. Recent
advances in immunology establish that environmental factors, including dietary micronutrients, actively
participate in modifying a variety of immune responses and influence the susceptibility of experimental animals
and humans to autoimmune and inflammatory diseases. The role of dietary micronutrients in GVHD
pathogenesis is poorly understood. We and others recently identified retinoic acid (RA), the active metabolite
of vitamin A, as a key molecule in facilitating the development of intestinal GVHD. These studies reveal how
the metabolite of a single common vitamin can profoundly influence GVHD risk after allogeneic HSCT. These
findings prompted us to examine the potential role of other dietary micronutrients in modulating the alloimmune
response. The objective of this grant is to define how vitamin D influences the development of GVHD. We will
test the novel hypothesis that enhancing intestinal vitamin D receptor (VDR) signaling strengthens mucosal
epithelial barrier to mitigate GVHD. This hypothesis is based on our exciting preliminary data demonstrating
that selectively enhancing intestinal VDR signaling protects against GVHD in experimental mice. We will
combine genetic, pharmacologic, and dietary approaches to examine this hypothesis. Studies in Aim 1 will
define the role of intestinal epithelial VDR signaling in modulating alloimmunity after HSCT. Aim 2 will
determine how therapeutic targeting of vitamin D/VDR pathway mitigates GVHD risk. We expect that results
from these studies will advance our understanding with respect to the role of vitamin D, as an environmental
factor, in GVHD pathogenesis. Furthermore, these studies will provide preclinical data that support the use of
vitamin D and its analogs as simple and cost-effective adjunct therapies with minimal side effects for GVHD
prevention and/or treatment.

## Key facts

- **NIH application ID:** 9894943
- **Project number:** 1R21AI144424-01A1
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Xiao Chen
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $246,500
- **Award type:** 1
- **Project period:** 2020-01-03 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9894943

## Citation

> US National Institutes of Health, RePORTER application 9894943, Targeting intestinal vitamin D receptor signaling to mitigate graft-versus-host disease (1R21AI144424-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9894943. Licensed CC0.

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