# Non-canonical functions of neutrophils

> **NIH NIH R01** · YALE UNIVERSITY · 2024 · $563,981

## Abstract

Project Summary
Tissue function demands the concerted function of specialized parenchymal cells, as well
as structural (vascular and mesenchymal) cell. Innate immune cells, such as macrophages
that populate and specialize in every organ, are now recognized actors in supporting tissue
function and long-term fitness. Only recently, neutrophils, the most abundant innate immune
leukocytes, have taken center stage and their functional diversity found important in the
context of disease. For example, low density neutrophils in cancer patients are a source of
angiogenic and immune-suppressive cues, whereas those that form NETs are a source of
autoantigens and chronic inflammation. In contrast to their contributions to disease, we have
pioneered studies showing that, like macrophages, neutrophils are part of normal tissue
homeostasis and that they can adapt to multiple environments in the healthy organism.
These new findings prompt the need to better understand how neutrophils adapt to the
different environments to fully grasp their contributions to homeostasis, and to determine the
extent to which they are co-opted by different types of disease. This is particularly relevant
in the context of acute or chronic inflammation, as perturbations of specific neutrophil fates
in organs may compromise tissue fitness, and increase the susceptibility to disease. The
overarching goal of this proposal is to understand the mechanisms that shape neutrophil
fates in tissues as a first step to define their actual contributions to organismal physiology
beyond immune defense. In the long term, we ambition to use this knowledge to build
precision medicine based on the remarkable plasticity of these cells.
To achieve these goals, we will first focus on the lung as model organ to define how
neutrophils naturally acquire angiogenic properties using mouse genetics, and the
consequences of disrupting this program in tissue repair (Aim 1). We will then query how
neutrophils acquire a surprising matrix-producing signature in barrier tissues, and use
biomechanical and imaging tools to define the contribution of this program to barrier integrity
and repair in the skin (Aim 2).

## Key facts

- **NIH application ID:** 10843277
- **Project number:** 5R01AI165661-03
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Andres Hidalgo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $563,981
- **Award type:** 5
- **Project period:** 2022-06-16 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10843277

## Citation

> US National Institutes of Health, RePORTER application 10843277, Non-canonical functions of neutrophils (5R01AI165661-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10843277. Licensed CC0.

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