# Functional Immunoimaging in the GI Tract

> **NIH VA IK2** · VETERANS HEALTH ADMINISTRATION · 2021 · —

## Abstract

There are limited effective treatments for autoimmune and inflammatory diseases in the GI tract like
Inflammatory Bowel Disease. The treatments that are available can have toxic side-effects and part of
the barrier to developing better alternatives is that mucosal immunity remains incompletely
understood. During disease, there is a breakdown in the body's natural tolerance mechanisms and that
allows inflammation to progress unopposed. There is a growing body of evidence that supports a role
for regulatory T cells (Tregs) in suppressing these deleterious immune responses but these cells are not
fully understood and the cellular dynamics have not been explored. In this application, we propose to
use functional immunoimaging to study Tregs as they modulate inflammation in the intestine and
explore the role of biotin and calcium in this process. There are several additional approaches to define
phenotype and functional status of the tissue and cells being studied which will supplement the imaging
findings. Notably, there are no published reports on studying Tregs in this manner during colitis. The
experiments have been designed to use two mouse models for colitis, an adoptive-transfer model and a
spontaneous model that develops with biotin deficiency. The experiments have also been developed in
such a way as to facilitate translation to the clinic. We will use two-photon microscopy which allows
for real-time imaging of lymphocytes interacting in live tissue to define the cellular immunoregulatory
events that explain how Tregs function to suppress colitis. In the first aim of the proposal, our studies
are focused on the mesenteric lymph node to look at induction and progression of immune responses
hypothesizing that Tregs physically displace pathogenic T cells from Dendritic Cells. We will also
perform experiments using an S1P1 agonist which is a pharmacological agent believed to prevents
effector T cells from leaving the lymph node and which may work synergistically with Tregs to prevent
pathogenic T cells from reaching the colon. A similar agent has already shown promising results in
clinical trials for Ulcerative Colitis. In the second aim of the proposal, our studies focus on the intestinal
wall where inflammation and tissue destruction create the disease symptoms. Again, we will be focused
on the role of Tregs in this process. We have seen that biotin deficient mice develop spontaneous disease
that completely resolves with biotin replacement which directly links biotin to intestinal inflammation.
If biotin supplementation can be shown to be effective, it would represent a low cost treatment without
side-effects. Finally, the third aim focuses on how Tregs modulate calcium signaling in effector T cells
in both the mesenteric lymph node and the colon. Calcium signaling is necessary for T cells to develop
an immunological synapse with Dendritic Cells for activation and pathogenesis. We believe that Tregs
hijack this process to induce the release of ...

## Key facts

- **NIH application ID:** 10046292
- **Project number:** 5IK2BX003518-04
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Jonathan Skupsky
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-10-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10046292

## Citation

> US National Institutes of Health, RePORTER application 10046292, Functional Immunoimaging in the GI Tract (5IK2BX003518-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10046292. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*