# Investigating a Role for Antigen Presentation by Enteric Glial Cells in Experimental Autoimmune Encephalomyelitis

> **NIH NIH F31** · UNIVERSITY OF VIRGINIA · 2024 · $40,205

## Abstract

PROJECT SUMMARY
 Multiple Sclerosis (MS) is a complex neurological disorder mediated by a T cell driven autoimmune attack
against myelin in the Central Nervous System (CNS). There is a correlation between MS and Inflammatory Bowel
Disorders (IBDs), as studies suggest that patients with IBDs have an increased risk of developing MS.
Furthermore, patients with MS commonly present with gastrointestinal symptoms which frequently precede MS
diagnosis. Together, these observations suggest that the gut may play a key role in the etiology of MS. Enteric
glial cells (EGCs) are observed throughout the gastrointestinal tract where they closely associate with neurons
and immune cells. Our increased understanding of glial functions in the Central Nervous System (CNS) has
demonstrated their profound influence on neurological disorders. EGCs bear resemblance to CNS glia, although
they are understudied in the context of neurological disorders which impact the gut, such as MS. EGCs are
equipped to respond to inflammatory cues, as they express several immune receptors and cytokines, as well as
antigen presentation machinery. It is compelling to speculate an enteric glial origin of MS, as these represent the
only cell type to express myelin proteins in the gut – a highly dynamic environment prone to inflammation and
rich in neuroimmune interactions. Given their potential role as antigen presenting cells (APCs) and expression
of myelin proteins, it is reasonable to speculate that intestinal inflammation such as that seen in IBDs could drive
EGCs could promote myelin-autoreactive T cell activation with the potential to spread into the CNS.
 The overall goal of this proposal is to characterize T cell responses against EGCs in the Experimental
Autoimmune Encephalomyelitis model of MS, as well as assess how EGC ablation impacts disease onset and
severity. The central hypothesis of this proposal is that suppressing autoreactive T cell responses driven in
response to EGC myelin antigen(s) in the gut during EAE is protective against intestinal and CNS pathology.
This hypothesis is supported by preliminary work described in this proposal which demonstrates a putative role
for EGCs in contributing to the peripheral immune response during EAE. The proposed experiments described
outline a plan to further characterize T cell responses against EGCs in a relapsing remitting EAE model (Aim 1)
and determine the impact of EGC ablation on EAE severity (Aim 2). This work could lend to a deeper appreciation
of MS etiology/pathology and the identification of novel therapeutic targets.

## Key facts

- **NIH application ID:** 10825729
- **Project number:** 1F31AI176816-01A1
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Ryan Brown
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $40,205
- **Award type:** 1
- **Project period:** 2024-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10825729

## Citation

> US National Institutes of Health, RePORTER application 10825729, Investigating a Role for Antigen Presentation by Enteric Glial Cells in Experimental Autoimmune Encephalomyelitis (1F31AI176816-01A1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10825729. Licensed CC0.

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