# Myeloid reprogramming in response to acute radiation tissue damage

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $349,713

## Abstract

We have discovered the striking emergence of a novel subpopulation of myeloid cells after whole body and
local irradiation that expresses both granulocytic (Ly6G) and monocytic (Ly6C) lineage markers at high levels.
This immature phenotype is not normally evident in peripheral organs at baseline but is mobilized from bone
marrow myeloerythroid progenitor cells. Their phenotype suggests that they may be granulocyte-derived
myeloid suppressor cells, as does their co-expression of PDL-1, PD-1, and CD39. We hypothesize that they
are an endogenous mechanism to minimize collateral damage from radiation-induced tissue damage and
inflammation. Importantly, depletion of this subset increases vulnerability to hematopoietic acute radiation
syndrome in mice and obliterates the action of radiation mitigator drugs that we have tested.
Our goal is to illuminate the fate and function of these myeloid cells and the role they play in acute and chronic
radiation tissue damage in animal models. We are mindful that myeloid cells tend to be exquisitely sensitive to
rapidly changing environments and that their phenotype and function adapt accordingly; in keeping with the
plasticity that is a hallmark of this lineage. Our hypothesis is that these cells sense and respond to damage-
associated molecules and cytokines released in the aftermath of radiation exposure, that they feed back to the
bone marrow driving self-sustaining loops of inflammation and myeloid lineage reprogramming which skews
the immune balance away from lymphopoiesis and towards myelopoiesis. In the long term, persistent myeloid
skewing affects hematopoiesis and perhaps function of other organs. The most likely culprit for mediating this
rapid radiation-induced myeloid surge is IL-6, but other factors are probably important. We will pursue these
avenues using a tool box of multi-color flow cytometry, Ly6G-depleting antibody, adoptive cell transfer and loss
of function genetic mouse models that will allow us to finely dissect the role of this response in acute and late
radiation damage. As part of the study, we will verify if these cells have inherent radiation mitigating
capabilities. Finally, these cells persist systemically and probably contribute to delayed normal tissue and
tumor responses to radiation therapy. We will therefore determine how they might shape persistent
inflammatory states and immune dysfunction.
With these studies we hope to gain a deeper understanding of the interactions between radiation tissue
damage, immune responses and the recovery processes with the ultimate goal of reprogramming the myeloid
system to better aid balanced normal tissue recovery after localized and whole body radiation exposures.

## Key facts

- **NIH application ID:** 10375367
- **Project number:** 5R01CA226875-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Dorthe Schaue
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $349,713
- **Award type:** 5
- **Project period:** 2019-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10375367

## Citation

> US National Institutes of Health, RePORTER application 10375367, Myeloid reprogramming in response to acute radiation tissue damage (5R01CA226875-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10375367. Licensed CC0.

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