# Neuroinflammation-induced lymphangiogenesis in the CNS

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $376,140

## Abstract

PROJECT SUMMARY/ABSTRACT
Adaptive immunity in most tissues of the body involves the drainage of antigens or antigen presenting cells within
conventional lymphatic vessels to the draining lymph nodes where antigen is presented to T cells. However,
there are no conventional lymphatic vessels within the CNS parenchyma. Alternatively, it has been hypothesized
that antigens, antigen presenting cells, and CSF may drain from the CNS into lymphatics near the cribriform
plate or dura to maintain fluid homeostasis and antigen drainage during steady-state conditions, yet little is known
about the role of these lymphatic vessels during neuroinflammation.
We discovered that lymphatic vessels near the cribriform plate undergo extensive in situ neo-lymphangiogenesis
during experimental autoimmune encephalomyelitis (EAE), a mouse model of Multiple Sclerosis. Our preliminary
data show that these neo-lymphatic vessels near the cribriform plate are functionally able to drain both CSF and
cells that were once in the CNS parenchyma. We further found the during EAE, VEGFC protein is produced by
infiltrating macrophages and dendritic cells to promote VEGFR3 dependent neo-lymphangiogenesis near the
cribriform plate. These data are the first to describe neo-lymphangiogenesis near the cribriform plate during
neuroinflammation. The long-term objective of this project is to characterize the functionality and contribution
of newly formed lymphoid vessels near to the cribriform plate to autoimmunity and stroke of the CNS.
The specific objectives of this proposal are (1) to define the characteristics and regulatory mechanisms driving
neo-lymphangiogenesis near the cribriform plate (Aim 1); (2) to test the functionality of neo-lymphatic vessels
near the cribriform plate and compare them to different CNS area lymphatics (Aim 2); and (3) to understand the
translational value of exacerbating or inhibiting neo-lymphangiogenesis near the cribriform plate in order to treat
CNS diseases (Aim 3).
Pharmacological inhibition or exacerbation of neo-lymphangiogensis to modulate pathology in CNS diseases
may have potential therapeutic values for CNS autoimmunity and ischemic trauma.

## Key facts

- **NIH application ID:** 10449330
- **Project number:** 5R01NS108497-05
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Zsuzsanna Fabry
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $376,140
- **Award type:** 5
- **Project period:** 2018-09-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10449330

## Citation

> US National Institutes of Health, RePORTER application 10449330, Neuroinflammation-induced lymphangiogenesis in the CNS (5R01NS108497-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10449330. Licensed CC0.

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