# Investigating the role of Akkermansia muciniphila and intestinal IL-17RA signaling in autoimmune inflammation

> **NIH NIH R21** · STATE UNIVERSITY NEW YORK STONY BROOK · 2020 · $235,951

## Abstract

Multiple Sclerosis (MS) is a devastating disease which desperately needs more effective prevention and
treatment. MS patients have dysregulated immune responses (GM-CSF, IL-17A and IFNg) as well as alterations
in the gut microbiota (increased prevalence of Akkermansia muciniphila) compared to healthy adults.
Additionally, findings in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, strongly
suggest that the gut microbiota are involved in disease pathogenesis. However, how the gut microbiota including
Akkermansia muciniphila (A. muciniphila) influences central nervous system (CNS) autoimmunity remains poorly
understood. IL-17A derived from Th17 cells (a,b T cells producing IL-17A and IL-17F) is thought to be a pro-
inflammatory cytokine implicated in EAE/MS, but IL-17A also has a beneficial effect in the gut. This differential
role of IL-17A in gastrointestinal versus systemic autoimmunity remains unclear. We were first to demonstrate
that IL-17A receptor (IL-17RA)-mediated epithelial cell signaling controls microbiota colonization. We found that
abrogation of intestinal IL-17RA function contributes to commensal dysbiosis, dysregulated immune cell
responses, and predisposition to autoimmunity. However, how intestinal IL-17RA regulation of microbiota
modulates systemic autoimmunity remains unclear. The objective of this proposal is to characterize the role of
the IL-17A-microbiome including A. muciniphila-CNS axis in regulating autoimmune inflammation, particularly
EAE. We have accumulated novel data that lack of intestinal IL-17RA signaling leads to commensal dysbiosis,
dysregulated GM-CSF responses as well as an enhanced susceptibility to EAE. Thus, based on our exciting
preliminary data, in Aim 1 we propose to investigate how enteric IL-17RA regulation of the microbiome controls
EAE. In Aim 2, we will determine whether A. muciniphila dysbiosis regulates fatty acid metabolites,
encephalitogenic GM-CSF responses as well as EAE incidence and score in our novel gut epithelial-specific IL-
17RA knockout mice. Upon completion, we will understand the mechanisms for microbiota-Th17 axis in
regulating neuroinflammation.

## Key facts

- **NIH application ID:** 9944454
- **Project number:** 5R21AI146696-02
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Pawan Kumar
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $235,951
- **Award type:** 5
- **Project period:** 2019-06-05 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9944454

## Citation

> US National Institutes of Health, RePORTER application 9944454, Investigating the role of Akkermansia muciniphila and intestinal IL-17RA signaling in autoimmune inflammation (5R21AI146696-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9944454. Licensed CC0.

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