# Transcriptional Regulation of Migrating Neutrophils during Pneumonia

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2021 · $412,500

## Abstract

Project Summary/Abstract
Pneumonia remains a significant cause of morbidity and mortality, which has come into sharp focus recently
during the COVID-19 pandemic. The lung is immunologically unique, and neutrophils traversing the lungs must
be ready to respond to potential pathogen challenges without causing injury to surrounding tissues. Disruptions
of this balance lead to many severe complications of pneumonia, but we lack therapeutics directed toward
neutrophil-mediated immune dysfunction. Our preliminary data demonstrate that neutrophils undergo
transcriptional remodeling as they travel from the circulation to the alveolar space during pneumonia. A subset
of pro-inflammatory genes is upregulated as neutrophils move from the vasculature to the interstitium, while
genes related to metabolism and degranulation are upregulated as cells move from interstitium to the alveolar
space. Maintenance of appropriate neutrophil function and development requires tight regulation of gene
changes, yet the specific pathways underlying such changes constitute a major knowledge gap. The goal of
this proposal is to delineate the transcriptional and functional changes neutrophils undergo as they migrate
from the circulation to the site of infection during pneumonia. Our central hypothesis is that during
pneumonia, appropriate neutrophil function is achieved by proscribed responses to specific
environmental stimuli, resulting in a heterogenous population defined by their interaction history.
Aim 1: Test the hypothesis that location-specific neutrophil responses in pneumonia are achieved by the tuning
of neutrophil transcriptome and function by environmental stimuli. Using complementary in vitro and in vivo
models we will determine the contributions of migration, pathogen interaction and cytokine signaling to
neutrophil gene programs and function. Outcomes will include transcriptional and functional changes predicted
by our preliminary studies. These findings will then be confirmed in an in vivo model of pneumonia, employing
exogenously added labeled neutrophils. Aim 2: Test the hypothesis that during transit to the alveolar space,
neutrophils differentiate into subpopulations unique to the lung, with transcriptional and functional
heterogeneity. Using a combination of in vivo cell labeling, flow cytometry assisted cell sorting, and single cell
RNA sequencing, we will track modulations in the neutrophil transcriptome from circulation to alveolar space at
a single cell level. Aim 3: NFκB-RelA is a central transcription factor in neutrophils, driving the upregulation of a
pro-inflammatory transcriptional program during migration to the alveolar space. Using complementary in vitro
and in vivo loss-of function models we will determine the effect of neutrophil NFκB-RelA on pneumonia
outcomes neutrophil transcriptome and neutrophil function. The results of these studies will have a positive
impact the field of pneumonia biology furthering our knowledge of neutrophil functi...

## Key facts

- **NIH application ID:** 10278158
- **Project number:** 1R01HL158732-01
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Katrina Traber
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $412,500
- **Award type:** 1
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10278158

## Citation

> US National Institutes of Health, RePORTER application 10278158, Transcriptional Regulation of Migrating Neutrophils during Pneumonia (1R01HL158732-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10278158. Licensed CC0.

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