# Supplement: Vitamin D Fluctuations and the Mucosal Immune Response

> **NIH NIH R01** · PENNSYLVANIA STATE UNIVERSITY, THE · 2020 · $40,684

## Abstract

SUMMARY PARENT AWARD
The vitamin D hypothesis proposes that vitamin D regulates gastrointestinal homeostasis by multiple
mechanisms and that changes in vitamin D status affect the composition of the microbiota, the development of
the immune response, clearance of gastrointestinal infections and the ability to reinstate homeostasis following
injury or infection. During the last grant cycle we determined several novel mechanisms by which vitamin D
regulated T cells to control homeostasis in the gut. Our new preliminary data demonstrate that disruptions in the
microbiota would inhibit vitamin D regulation of immune function and the metabolism of vitamin D by the host.
These novel areas of investigation serve as the focus of the present application.
The gastrointestinal immune system is a population of heterogeneous cells whose role is to maintain ignorance
of the large number of antigens present in food as well as the microbiota. The microbiota in turn shapes the
immune response. Germfree mice have reduced B cell IgG1, IgG2a and IgA responses, but hyper-IgE
antibodies. Hyper-IgE is a symptom of dysbiosis and a failure of homeostasis. Vitamin D deficient and vitamin
D receptor knockout mice have hyper-IgE and dysbiosis of the microbiota. In addition, following injury vitamin D
regulates the T and B cell response in part through regulation of the microbiota. Perturbations of homeostasis,
following gastrointestinal infection, of vitamin D deficient mice was severe and associated with the reduced
production of antigen specific antibody responses. Not only was there an effect of vitamin D on the microbiota
but the microbiota affected vitamin D metabolism. This proposal will focus on the effects of vitamin D on B cells
and the microbial interactions that control the B cell response and microbial regulated tissue vitamin D
metabolism. Our novel central hypothesis is that “Vitamin D and the microbiota cooperate to regulate B cells
and the vitamin D responsiveness of the host.”
The three aims are:
Aim 1: Determine the direct and indirect targets of vitamin D on B cells in vivo that are important for
maintaining homeostasis, induction of antibody responses, and protection from GI infection.
Aim 2: Determine which of the effects of vitamin D depend on the microbiota.
Aim 3: Determine the role of the microbiota in the induction of 24,25(OH)2D by B cells.
SUMMARY ADMINISTRATIVE SUPPLEMENT.
This administrative supplement would be used to do some important experiments in gnotobiotic mice that were
not possible until recently. We would like to rederive a Cyp27B1 reporter strain as germfree. Cyp27B1 is the
key enzyme controlling production of 1,25(OH)2D. These germfree Cyp27B1 ko/+ and ko/ko reporter mice will
then be immunized or colonized with a single microorganism (one commensal and one pathogen) to determine
which immune or microbial signals induces expression of Cyp27B1 in B cells or other immune cells. At the
completion of these experiments we will definitive...

## Key facts

- **NIH application ID:** 10024854
- **Project number:** 3R01AT005378-09S1
- **Recipient organization:** PENNSYLVANIA STATE UNIVERSITY, THE
- **Principal Investigator:** MARGHERITA T CANTORNA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $40,684
- **Award type:** 3
- **Project period:** 2009-08-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10024854

## Citation

> US National Institutes of Health, RePORTER application 10024854, Supplement: Vitamin D Fluctuations and the Mucosal Immune Response (3R01AT005378-09S1). Retrieved via AI Analytics 2026-05-31 from https://api.ai-analytics.org/grant/nih/10024854. Licensed CC0.

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