# Ly6 family members in neutrophil biology

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $340,287

## Abstract

Project Summary
Neutrophils protect against infection but also mediate inflammatory tissue injury. As a result,
targeting neutrophils therapeutically will require a detailed understanding of their basic biology,
focused on domains wherein the defensive and pathogenic functions of neutrophils may diverge.
In the first cycle of the present award, we explored two related GPI-linked neutrophil surface
proteins of poorly-characterized function, Ly6G in mice and CD177 in humans. We showed that
both associate at a molecular level in cis with neutrophil surface β2 integrins and that their ligation
thereby attenuates neutrophil migration. Taking advantage of the experimental potential of murine
inflammatory models, we found that Ly6G ligation selectively reduced integrin-mediated migration
typical for neutrophil diapedesis toward sterile triggers, leaving integrin-independent migration to
infectious stimuli largely unperturbed. Our preliminary data now show that Ly6G differentiates
subphenotypes within murine neutrophils, while in humans CD177pos and CD177neg neutrophils
differ in gene expression and potentially cytokine production. Together with the productivity of the
first cycle of the award, these findings support deeper investigation of the role of these Ly6-family
molecules in neutrophil biology.
We propose two new and independent specific aims. Aim I pursues the mechanisms by which
Ly6G and CD177 alter neutrophil β2 integrin function, including a search for novel endogenous
counterligands. Aim II develops preliminary RNAseq data distinguishing neutrophil subtypes based
on expression of Ly6G and CD177, from healthy donors as well as from adults and children with
inflammatory arthritis and the transient but intensely inflammatory vasculitis Kawasaki disease.
Together, these studies will advance the understanding of neutrophils by defining how Ly6 family
members regulate 2 integrins to control cell migration and by identifying neutrophil phenotypes
reflected in differential expression of Ly6G and CD177.

## Key facts

- **NIH application ID:** 9971888
- **Project number:** 2R01AR065538-06A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Peter A Nigrovic
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $340,287
- **Award type:** 2
- **Project period:** 2014-07-08 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971888

## Citation

> US National Institutes of Health, RePORTER application 9971888, Ly6 family members in neutrophil biology (2R01AR065538-06A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9971888. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*