# Alarmin-mediated control of CNS infection

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2020 · $316,228

## Abstract

PROJECT SUMMARY
The funded award (R01NS112516) focuses on the role of alarmins in activating innate immune responses in
the brain. My laboratory has studied the role of two alarmins, IL-1a and IL-33, that independently trigger
inflammation and protective immunity against a brain infection. Interestingly, IL-1a and IL-33, share a co-
receptor, interleukin-1 receptor accessory protein (IL-1RAP). Of relevance to Alzheimer’s Disease (AD) and the
basis of this administrative supplement application, SNPs in il1rap have been associated with AD progression,
the accumulation of amyloid plaques, and decreased inflammation in the brain. These findings also implicate
the role for alarmins that bind and signal through IL-1RAP (IL-1, IL-33, and the lesser studied IL-36 family
members), molecules expressed in healthy cells that are released upon cell death and initiate local
inflammation. Of note, genome-wide association studies have also implicated SNPs in il1a and il33 in AD, but
to a lesser degree. Taken together, several human genetic studies have implicated aberrant alarmin sensing in
the progression of AD. My laboratory has been studying the expression, sensing, and importance of alarmins
in the brain for several years. We have an extensive understanding of how these molecules promote immunity
to infection and have unique tools to understand alarmin biology in AD. Importantly, we find that alarmins
activate the brain to promote the entry of peripheral immune cells to the CNS during infection, especially
phagocytic monocyte-derived macrophages. We hypothesize that alarmin signaling is necessary to facilitate
enhanced phagocytosis in the AD brain. To test this hypothesis, we propose three aims that mirror those of the
funded application.

## Key facts

- **NIH application ID:** 10120929
- **Project number:** 3R01NS112516-01S2
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** TAJIE H. HARRIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $316,228
- **Award type:** 3
- **Project period:** 2020-02-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10120929

## Citation

> US National Institutes of Health, RePORTER application 10120929, Alarmin-mediated control of CNS infection (3R01NS112516-01S2). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10120929. Licensed CC0.

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