# The Role of TRPV4 in central nervous system immunity and disease

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2021 · $401,701

## Abstract

Abstract
Experimental autoimmune encephalomyelitis (EAE) is a CD4 T cell-dependent model for
the human disease multiple sclerosis (MS). In these diseases, a complex immune
response is orchestrated toward central nervous system (CNS) myelin. Ultimately, the
cascade of inflammatory events culminates in myelin and neuronal damage, mediated in
large part by phagocytic immune cells such as infiltrating macrophages and activated
microglia. The molecular regulation that governs inflammatory responses by these
innate cell subsets remains unclear. In preliminary studies, we have discovered that the
Transient Receptor Potential (TRP) cation channel, TRPV4 is expressed by microglial
cells and functions to propagate effector inflammatory responses during EAE. These
data have led us to hypothesize that expression of TRPV4 by innate immune cells,
including circulating monocytes and microglia, contributes to the pathogenesis of MS
and can be modulated to reduce the severity of neuro-inflammation. We will employ
three complementary aims to explore this hypothesis. First, we will determine the cellular
basis of TRPV4-mediated neuro-immune interactions in the CNS using both radiation
bone marrow chimeras and a new murine reagent we have designed in which TRPV4 is
conditionally expressed in vivo. Second, we will determine the therapeutic effect of
TRPV4 inhibition during EAE. Third, we will examine human tissue and material from an
extensive bio-repository to assess the expression of TRPV4 in immune cells and MS
lesions. This highly translational study will establish the cellular mechanism of TRPV4-
dependent immune activation during EAE, the potential for pharmacologic modulation of
neuro-inflammation via TRPV4, and the pattern of TRPV4 expression in patients with
MS. Thus, this study engenders a unique opportunity to identify a molecular target for
the rational design of treatment for neuro-inflammatory diseases such as MS.

## Key facts

- **NIH application ID:** 10240568
- **Project number:** 5R01NS106289-04
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Gregory Wu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $401,701
- **Award type:** 5
- **Project period:** 2018-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10240568

## Citation

> US National Institutes of Health, RePORTER application 10240568, The Role of TRPV4 in central nervous system immunity and disease (5R01NS106289-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10240568. Licensed CC0.

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