# Understanding the roles type I Interferon and TH17 play in Neuromyelitis Optica and other autoimmune diseases.

> **NIH NIH R01** · OKLAHOMA MEDICAL RESEARCH FOUNDATION · 2021 · $700,785

## Abstract

Summary:
 Neuromyelitis optica (NMO) is a rare but devastating inflammatory disorder of the central nervous system
(CNS) that primarily affects the optic nerves and spinal cord. NMO was initially characterized as a subset of
multiple sclerosis (MS), but is now considered a distinct disease. It has been shown that both type I interferon
(IFN-I) and T helper 17 (TH17) cells play a critical role in the pathology of NMO, however it is unclear how IFN-I
and TH17 cooperate to drive disease pathology. Our preliminary data now show that IFN-I gene signatures are
elevated in blood from NMO and are highly correlated with TH17 signatures. Furthermore, our studies using
mice with TH17-induced experimental autoimmune encephalomyelitis (TH17-EAE) supports the hypothesis that
IFN-I fuels TH17-mediated disease by stimulating antigen presenting cells to produce IL-6 which in turn drives
the production of GM-CSF and other inflammatory cytokines. For this grant application, we propose to use NMO
patient samples and TH17-EAE to study how TH17 and IFN-I cooperate in driving neuro-inflammation in human
disease and in an in vivo animal model. In AIM 1, we will use RNA-sequencing to identify the discrete cell types
that harbor the IFN-I signature in NMO patients and discover novel genes that could regulate IFN-I and TH17
pathways. In Aim 2, we will perform in vitro culture experiments to determine how IFN-I affects T helper cell
differentiation in NMO patients compared to healthy controls. In Aim 3, we will use the TH17-EAE model to
understand the mechanisms by which IFN-I exacerbates TH17-induced neuro-autoimmune disease. The
combination of research on human subject and the mechanistic animal experiments outlined in this proposal
have the potential to give deep insight into pathological processes that underlie NMO and other autoimmune
diseases with IFN-I and TH17 signatures.

## Key facts

- **NIH application ID:** 10215451
- **Project number:** 5R01AI137047-04
- **Recipient organization:** OKLAHOMA MEDICAL RESEARCH FOUNDATION
- **Principal Investigator:** Robert C Axtell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $700,785
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10215451

## Citation

> US National Institutes of Health, RePORTER application 10215451, Understanding the roles type I Interferon and TH17 play in Neuromyelitis Optica and other autoimmune diseases. (5R01AI137047-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10215451. Licensed CC0.

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