# The Role of TREM-1 in the Regulation of Allergic Airway Inflammation

> **NIH VA I01** · IOWA CITY VA MEDICAL CENTER · 2024 · —

## Abstract

In the last 20 years more than 3 million United States military personnel have been deployed overseas and
emerging evidence suggests that deployed personnel have a much greater risk of developing respiratory
diseases such as asthma. Among Veterans Affairs patients who were deployed to Iraq and Afghanistan,
asthma prevalence nearly tripled. Studies conducted by the Department of Defense analyzing military
encounter data demonstrate increased encounters occur for respiratory symptoms, predominantly asthma,
after deployment. One potential explanation is that U.S. military personnel deployed in Southwest Asia and
Afghanistan experience elevated exposures to particulate matter (PM) and other inhalational exposures
including desert dust and burn pit combustion. In particular deployed troops are exposed to diesel fuel
which is extensively used in ground equipment and in many tracked and wheeled vehicles. Thus,
understanding how inhalational exposures trigger allergic airway inflammation (AAI), whether this is
exacerbation of existing disease or precipitation of de novo disease, is a critical need in military population.
Allergen sensitized TH2 cells are required but not sufficient for the development of the allergic asthma
phenotype. It is clear from the literature that not all allergic individuals develop asthma upon allergen
exposure, despite systemic sensitization to airborne allergen. In this application we present compelling
preliminary data that neutrophils promote pathogenic T cell response in the airway following inhalational
challenge.
Triggering Receptor Expressed on Myeloid Cell-1 (TREM-1), exclusively expressed on human neutrophils
and monocytes, serves as a global regulator of immune responses. TREM-1 synergizes with Toll-like
receptors, Nod-like receptors, and damage-associated molecular patterns to increase inflammation in
response to inhalational exposures. We hypothesize that neutrophils modulate T cell responses to allergens
in the airspace in a TREM-1 dependent manner. This hypothesis is built upon a growing body of literature
that demonstrate that neutrophils have an important role in the pathogenesis of AAI and our strong
Preliminary Data in TH2 dominant AAI. We demonstrate that neutrophils are present in high numbers
immediately following allergen challenge in asthmatic subjects’ airways, that expression of neutrophil
receptor TREM-1 exacerbates TH2 dominant AAI in vivo, and that neutrophils modulate T cell cytokine
production in a TREM-1 dependent manner.
In our Preliminary Data, we identify a novel TREM-1 dependent interaction between neutrophils and T cells
that may shed light on the mechanism responsible for the large increase in AAI following exposure to
airborne hazards in military populations. Using a TH2 dominant AAI model, Cre recombinase systems, and
adoptive transfer, we will determine how TREM-1 promotes AAI severity as measured by airway
hyperreactivity, cellular quantification by flow cytometry, cytokine levels, and h...

## Key facts

- **NIH application ID:** 10700464
- **Project number:** 1I01BX005989-01A2
- **Recipient organization:** IOWA CITY VA MEDICAL CENTER
- **Principal Investigator:** JULIA A KLESNEY-TAIT
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2024-01-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10700464

## Citation

> US National Institutes of Health, RePORTER application 10700464, The Role of TREM-1 in the Regulation of Allergic Airway Inflammation (1I01BX005989-01A2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10700464. Licensed CC0.

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