Investigating periostin-mediated T cell recruitment and muscle fibrosis in peripheral neuropathy

Active Project Grant Awarded Last action

Award ID
F31NS147716
Recipient
Awarding agency
Obligated
$74,498

Award facts

Completion date 0% complete
Originally
Place of performance
St. Louis, MO 63110, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Peripheral neuropathy is the most common type of neurodegenerative disease, affecting millions of people and leading to progressive motor deficits. While various forms of neuropathy exist, a unifying feature is axon degeneration, which ultimately disrupts nerve function and compromises mobility. Alongside axon degeneration, muscle wasting emerges as a major consequence of peripheral neuropathy, further compounding disability. Understanding the mechanisms driving axon degeneration and its downstream consequences is essential for developing therapies to mitigate neurological disease burden; such goal aligns with the mission of the national institute of neurological disorders and stroke (NINDS). The enzyme SARM1 is the central executioner of axon degeneration: IT is both necessary and sufficient to initiate an intrinsic axon destruction program following injury. Chronic SARM1 activation leads to persistent neuroinflammation and progressive functional decline prior to aberrant axon degeneration, a pathological state termed "sarmopathy." this study uses a mouse model of sarmopathy, derived from a human case of chronic peripheral neuropathy. Notably, macrophage or T cell depletion from sarmopathic mice restores motor function, suggesting that neuroimmune interactions play a key role in driving disease. The mechanisms linking chronic SARM1 activation to immune cell recruitment, axon degeneration, and muscle deterioration remain unresolved. This project aims to uncover periostin (POSTN) as the molecular bridge between SARM1 activation and T cell recruitment in sarmopathy. Periostin is an extracellular matrix (ECM) protein widely recognized as a biomarker of fibrosis, a pathological process implicated in neurodegenerative diseases, where excessive ECM deposition impairs motor function. Beyond its fibrotic role, periostin is also a regulator of immune cell recruitment, with its secretion promoting immune infiltration across a range of disease contexts. Thus, this project seeks to determine whether periostin links SARM1 activation to both T cell infiltration and muscle fibrosis. Aim 1A determines whether periostin is required for T cell recruitment in sarmopathic nerves by analyzing immune cell populations in the sciatic nerves of periostin-knockout sarmopathic mice using immunohistochemistry and full-spectrum flow cytometry. To assess whether periostin's role extends beyond chronic SARM1 activation, this sub-aim also uses the sciatic nerve crush model as an acute, SARM1-dependent injury paradigm to evaluate whether periostin similarly drives T cell infiltration in other contexts of SARM1 activation. Aim 1B examines whether periostin from schwann cells is sufficient to drive this process. Aim 2 examines periostin's role in fibrosis and motor decline by assessing fibrotic markers like collagen through masson's trichrome stain and western blot analysis. Additionally, we will evaluate functional outcomes through muscle strength tests, such as the grip strength test. This project may uncover periostin as a mediator of muscle wasting and T cell recruitment into the nervous system, establishing a therapeutic target for limiting neuroinflammation, preserving muscle health, and mitigating disease progression.

Transactions

Action Obligated Date
Amendment $0
Original award $37,249

Quick answers

Who received award F31NS147716?

F31NS147716 was awarded to The Washington University by National Institute of Neurological Disorders and Stroke (National Institutes of Health) on December 1, 2026.

How much is award F31NS147716 worth?

$74,498 has been obligated on F31NS147716.

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