Investigating a role for antigen presentation by enteric glial cells in experimental autoimmune encephalomyelitis

Ended Project Grant Awarded Last action

Award ID
F31AI176816
Recipient
Awarding agency
Obligated
$157,730

Award facts

Assistance listing
93.855 Allergy and Infectious Diseases Research
Completion date
Place of performance
Virginia, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
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.

Transactions

Action Obligated Date
Amendment -$530
Amendment $0
Amendment $1,280
Amendment $1,280
Amendment $38,925
Amendment $0
Amendment $38,925
Amendment $0
Amendment $38,925
Amendment $0
Original award $38,925
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Quick answers

Who received award F31AI176816?

F31AI176816 was awarded to Rector & Visitors Of The University Of Virginia by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on September 14, 2024.

How much is award F31AI176816 worth?

$157,730 has been obligated on F31AI176816.

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