# Adaptive Immune Regulation of Traumatic Injury

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $414,636

## Abstract

PROJECT SUMMARY
Traumatic injuries disrupt immune system homeostasis, which can predispose patients to opportunistic
infections and other trauma-associated complications like systemic inflammatory response syndrome (SIRS),
organ damage, and chronic critical illnesses. Trauma induces unique and complex host responses that are
initiated by tissue damage and the release of danger-associated molecular patterns (DAMPs) that trigger
specific immune reactions. We identified that a subset of CD4+ T cells called regulatory T cells (Tregs) are
acutely activated by injury in a mouse burn trauma model. The counter-inflammatory suppressive activity of
Tregs is enhanced by trauma, which suggests that Tregs may control the intensity of post-trauma inflammation
and restoration of immune system homeostasis. People can have different numbers of Tregs in their tissues or
have different functional Treg responses to trauma that could determine trajectory of their response to
traumatic injuries. Our hypothesis is that Tregs control immune reactions to DAMPs and influence the
trajectory of the host response to trauma. To address this hypothesis, we propose a series of trauma
immunology studies to systematically interrogate; 1) Treg control of immune system phenotypes and
homeostasis, 2) trauma-induced Treg activation mechanisms, and 3) effects of modulating Tregs on immune
phenotypes, anti-microbial immune function, and the two-hit SIRS response. The specific aims for this project
are; 1) To determine how CD4+ Tregs control immune system reactivity to trauma, 2) To define the specificity
and molecular nature of trauma-reactive CD4+ Tregs and other T cells, 3) To investigate how CD4+ Tregs
influence anti-microbial immunity and two-hit SIRS. We anticipate that the outcome of this research will
significantly advance our fundamental knowledge of specific immune mechanisms that modulate trauma
immunity. We have several significant goals that we wish to achieve during the course of this project; 1) to
provide new insights into the biology of Treg activation and function, 2) to develop a deeper understanding of
immune system control of the mammalian trauma response, and 3) to explore the therapeutic potential of
modulating Treg activation and function as a specific trauma immunotherapy to improve immune function and
balance following trauma.

## Key facts

- **NIH application ID:** 10415072
- **Project number:** 5R01AI148232-03
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** JAMES A. LEDERER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $414,636
- **Award type:** 5
- **Project period:** 2020-06-10 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10415072

## Citation

> US National Institutes of Health, RePORTER application 10415072, Adaptive Immune Regulation of Traumatic Injury (5R01AI148232-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10415072. Licensed CC0.

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