# Macrophage regulation of the erythron

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2021 · $474,261

## Abstract

Abstract
 The overall aim of this proposal is to bring together the respective expertise of the Elliott and Palis labs in
macrophage and erythroid biology, respectively, to better understand the role of bone marrow-resident
macrophages in the regulation red blood cell production. While great progress has been made recently in
understanding macrophage heterogeneity and tissue-specific function in many organs, including brain, skin,
lungs, intestines, liver, and spleen, comparatively little is known about the diversity of macrophages in the bone
marrow, where macrophages are key players in providing the microenvironmental niche for maturing erythroid
precursors within “erythroblastic islands.” In Aim 1, we will employ functional tests of multidimensional flow
cytometric data to better define the diversity of erythroid-associated macrophages (EA-Macs) in the bone
marrow. Adult humans synthesize 2.5 million new red blood cells every second to maintain our circulating red
cell mass, which constitutes >80% of all the cells in the body. Terminal erythroblasts in mammals enucleate to
yield reticulocytes and pyrenocytes. An important function of EA-Macs is pyrenocyte clearance via
phagocytosis. In Aim 2 we will test the function of CD47 “don't eat me” signals in the differential clearance of
pyrenocytes but not erythroblasts. In addition, we will investigate the role of erythropoietin, the primary
regulator of red cell production, in regulating the capacity of EA-Macs to clear pyrenocytes. Erythropoietin
promotes the survival of late stage erythroid progenitors and immature erythroblasts, which together constitute
the erythropoietin-responsive compartment of the erythron. Our preliminary studies in two independent-
radiation and phlebotomy- models of stress erythropoiesis indicate that erythropoietin expands the
erythropoietin-responsive compartment in the bone marrow in a macrophage-dependent manner. In Aim 3, we
will test the novel hypothesis that EA-Macs mediate recovery from acute anemia by critically regulating the
erythropoietin-responsive compartment. Taken together these studies will establish fundamental insights
regarding the microenvironmental regulation of the erythron by EA-Macs in the bone marrow and will lay the
groundwork for the future study of the role of EA-Macs in disease states of erythroid over- and under-
production.

## Key facts

- **NIH application ID:** 10214601
- **Project number:** 5R01DK119285-03
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Michael Rusty Elliott
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $474,261
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10214601

## Citation

> US National Institutes of Health, RePORTER application 10214601, Macrophage regulation of the erythron (5R01DK119285-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10214601. Licensed CC0.

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