# A novel regulator of extracellular nucleic acid sensing

> **NIH NIH R21** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2021 · $254,250

## Abstract

ABSTRACT
Pathogen-derived RNA represents a canonical pathogen-associated molecular pattern (PAMP), and its
detection by pattern recognition receptors (PRR) is a fundamental feature of innate immunity. Extracellular
RNA is detected primarily via endosomal Toll-like receptors (TLRs), including those detecting single-
stranded RNA (TLR7/TLR8) and double-stranded RNA (TLR3). Signaling through endosomal TLRs induces
the production of cytokines including type I interferons (IFN), which elicit antiviral states and broadly activate
the immune system. Sensing of both DNA and RNA is tightly regulated by nucleic acid-processing
enzymes, which may be required both to generate DNA/RNA ligands for recognition by PRRs, and to
prevent aberrant accumulation of nucleic acids. However, little is known about the enzymes that may control
extracellular RNA and its sensing by endosomal TLRs. We have identified a candidate enzyme that may
represent a negative regulator of TLR-mediated extracellular RNA sensing; as such, this protein may
dampen inflammation and tissue damage during antimicrobial immune responses, as well as restrict
autoreactivity in autoimmune disease. In Aim 1, we will use gain and loss-of-function approaches to test
how it affects the sensing of RNA and related PAMPs by endosomal TLRs. In Aim 2, we will test its role in
animal models of autoimmunity, as well as in antiviral immune responses. The proposed studies may help
identify a novel regulator of innate immune sensing and provide rationale for its development as a protein
therapeutic in inflammatory and/or autoimmune diseases.

## Key facts

- **NIH application ID:** 10234619
- **Project number:** 1R21AI161772-01
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Boris Reizis
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $254,250
- **Award type:** 1
- **Project period:** 2021-03-16 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10234619

## Citation

> US National Institutes of Health, RePORTER application 10234619, A novel regulator of extracellular nucleic acid sensing (1R21AI161772-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10234619. Licensed CC0.

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