# Pathologic Myeloid Activation in Pediatric Burn Injury

> **NIH NIH R21** · UNIVERSITY OF FLORIDA · 2023 · $190,625

## Abstract

ABSTRACT
Burn injury is a leading cause of trauma in children, resulting in life-long physical and psychological morbidities.
Young children, particularly those under 5-years of age, represent a highly vulnerable and at-risk population for
an exaggerated systemic host response leading to multiple organ system dysfunction (MODS). Unfortunately,
much of our current burn treatment strategies are extrapolated from adult studies or are broadly applied across
the age spectrum. These approaches fail to consider the unique host immune responses of pediatric patients
across the different age stages of childhood. Understanding age-specific immune dysfunction resulting from
pediatric burn injury will address a key gap of knowledge necessary to develop novel personalized interventions
for this highly vulnerable population. Our overarching hypothesis is that burn injury induces pathologic myeloid
activation in the pediatric host, resulting in expansion of myeloid-derived suppressor cells (MDSCs), suboptimal
monocyte function, lymphopenia and lymphocyte dysfunction. Additionally, we believe this effect is both age-
and burn size-dependent, such that younger patients more commonly enter a state of pathologic myeloid
activation with increased susceptibility to burn sepsis and immunosuppression. We have two specific aims: 1) to
determine whether pediatric burn injury leads to pathologic myeloid activation, increasing circulating
immunosuppressive MDSCs, engendering dysfunctional monocyte and decreasing lymphocyte numbers and
function; and, 2) to examine whether pediatric burn injury induces a unique blood myeloid and lymphoid
transcriptome in young and older pediatric patients with small and larger burns that can explain the functional
and phenotypic changes. To achieve these goals, we intend to enroll two pediatric burn patient cohorts differing
in their age and burn size. We intend to compare children 1–5 years old (n=30) with either small (<15% TBSA,
n=15) or larger (15-30% TBSA, n=15) burns, with children 9-15 years old (n=30) with TBSA-matched burn sizes
(n=15 each), and age-matched non-injured controls (n=30). Using flow cytometry, we will determine how MDSC
numbers and phenotypes are influenced by pediatric age and burn size over time. Similarly, we will investigate
MDSC numbers and function in relation to susceptibility to and loss of T-cell proliferation and IFNγ production
(ELISpot). Additionally, we will determine changes in blood monocyte HLA-DR expression, monocyte distribution
width (MDW) and quantify ex vivo stimulated mononuclear TNF-α production (ELISpot). In a subset of these
patients, we will perform single cell RNA-seq/CITE-Seq (Cellular Indexing of Transcriptomes and Epitopes by
Sequencing) of blood myeloid and lymphoid cells in the early (day 4) and later (day 30) periods after burn injury.
Our ultimate goal is to develop novel treatment paradigms that treat children with a personalized approach
ensuring that this vulnerable population “…ach...

## Key facts

- **NIH application ID:** 10673601
- **Project number:** 5R21HD107467-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Shawn David Larson
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $190,625
- **Award type:** 5
- **Project period:** 2022-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10673601

## Citation

> US National Institutes of Health, RePORTER application 10673601, Pathologic Myeloid Activation in Pediatric Burn Injury (5R21HD107467-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10673601. Licensed CC0.

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