# TARGETING INTERFERON LAMBDA SIGNALING DURING CENTRAL NERVOUS SYSTEM AUTOIMMUNITY

> **NIH NIH F31** · WASHINGTON UNIVERSITY · 2020 · $32,717

## Abstract

Project Summary/Abstract
The goal of this proposal is to elucidate the role of interferon lambda (IFNλ) during central nervous system (CNS)
autoimmunity. The most common form of CNS autoimmunity among humans is multiple sclerosis (MS), a disease
that affects over 2.5 million people worldwide2,16. MS is a demyelinating autoimmune disease that can cause a
variety of neurologic symptoms including extremity weakness, optic neuritis, and ataxia1; it is a major cause of
disability in young adults. Due to the young age of onset and continuously progressive nature of the disease, MS
is not only a personal burden but also a substantial socioeconomic burden16. Currently, there are approximately
one dozen therapeutic options for MS; although effective in reducing relapse frequency and severity, they have
numerous side effects and none actually halt disease progression or promote recovery19. This suggests the need
for an improved understanding of mechanisms driving chronic disease and to translate this information into new
therapeutic strategies for MS.
IFNλ (interferon lambda or type III IFN) is a class of cytokines closely related to type I IFN; both classes initiate
analogous JAK STAT signaling pathways that induce expression of antiviral genes8-10. Type I IFN have been
highly studied in CNS autoimmune diseases and play a protective role that is consistent with its use as a
therapeutic for MS12,13,31. Very little, however, is known about the role of IFNλ in MS. Preliminary data has
demonstrated that IFNλ may prevent recovery and lead to sustained inflammation in the murine model of CNS
autoimmunity, experimental autoimmune encephalomyelitis (EAE). Animals deficient in IFNλ signaling
demonstrated improved clinical scores, decreased inflammation, and decreased axonal damage during recovery
from EAE. This suggests that IFNλ may play a critical role in disease maintenance after disease is already
initiated. Therefore, the goal of this project is to understand how IFNλ modulates immune mediated
inflammation and neuronal damage during CNS autoimmunity. The studies outlined in this proposal include
experiments to analyze spatiotemporal expression of IFNλ and its receptor, to conditionally delete IFNλ receptor
in a cell specific manner, to analyze in vitro cultures of antigen presenting cells (APCs) and T cells, to examine
IFNλ’s effects on demyelination, and to measure IFNλ levels in MS patient samples. Completion of this project
will provide insights into the cellular mechanisms underlying CNS autoimmune diseases.

## Key facts

- **NIH application ID:** 9896666
- **Project number:** 5F31NS108629-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Sindhu Manivasagam
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $32,717
- **Award type:** 5
- **Project period:** 2019-03-11 → 2021-03-10

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9896666

## Citation

> US National Institutes of Health, RePORTER application 9896666, TARGETING INTERFERON LAMBDA SIGNALING DURING CENTRAL NERVOUS SYSTEM AUTOIMMUNITY (5F31NS108629-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9896666. Licensed CC0.

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