# Hematopoietic Stem and Progenitor Cell Dysfunction is an Underlying Mechanism of Injury-Inuced Immunosuppression

> **NIH NIH R35** · WASHINGTON UNIVERSITY · 2022 · $393,750

## Abstract

PROJECT SUMMARY-ABSTRACT
Critical illness is a leading cause of death in the United States. Critical illness results in persistent and
pervasive immune dysfunction, predisposing patients to infection. We hypothesize that the alterations in the
function of the hematopoietic stem and progenitor cells contributes to critical-illness induced
immunosuppression.
For over 25 years it has been recognized that critical illness can alter the function of hematopoietic stem and
progenitor cells (HSPC) in the bone marrow. Other studies have demonstrated that hematopoietic stem cells
(HSC) regulate the immuno-inflammatory response, altering the production and function of leukocytes derived
from these progenitors. We hypothesize that injury results in damage to the HSPC that results in changes in
the function of progeny leukocytes, contributing to injury-induced immune dysfunction. We present preliminary
data demonstrating that injury causes dramatic expansion of immature progenitors in the bone marrow through
IL-1 mediated production of G-CSF and that myeloid cells derived from the bone-marrow of injured mice have
a defective response to microbial products.
Here we propose a line of investigation to define the role of HSPC in injury-induced immune dysfunction and to
extend these results from the bench to the bedside. Key tasks of this proposal are 1. To directly link changes
in the hematopoietic stem cells with changes in innate immunity in murine models of critical illness and in
critically ill patients. 2. Define the mechanisms by which injury alters the function of the HSPC. 3. Determine
how injury-induced changes in the HSPC are propagated to the effector leukocytes.

## Key facts

- **NIH application ID:** 10441275
- **Project number:** 5R35GM133756-04
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** ISAIAH R Turnbull
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $393,750
- **Award type:** 5
- **Project period:** 2019-09-05 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10441275

## Citation

> US National Institutes of Health, RePORTER application 10441275, Hematopoietic Stem and Progenitor Cell Dysfunction is an Underlying Mechanism of Injury-Inuced Immunosuppression (5R35GM133756-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10441275. Licensed CC0.

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