# The Role of Erythroblastic Islands in Anemia of Inflammation

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2021 · $619,934

## Abstract

Project Summary/Abstract
Terminal erythropoiesis in mammals occurs within the erythroblastic islands (EBIs), niches where erythroblasts
differentiate in close interaction with a central (nursing) macrophage. Although EBIs were described in 1958
by Marcel Bessis as the first hematopoietic niche, there are still many questions to be answered to improve our
understanding of their structure and function.
Anemia of inflammation (AoI) occurs in patients with chronic or acute immune activation (due to an infectious,
malignant, or autoimmune disease) and affects the quality of life of millions of people worldwide.
The overall goal of this application is to understand the structure and function of the EBI as the erythropoietic
niche in normal, baseline erythropoiesis and how this is modified in conditions leading to anemia of
inflammation. Our preliminary data show that F4/80, VCAM1, and CD169 are expressed heterogeneously by
the central macrophages within the EBIs. In marked contrast, CD11b is low or negative on the EBI
macrophage, while it is abundantly present on other cells within the islands. The CD11b+ cells within EBIs are
granulocyte precursors in contact to the central macrophage (Mφ). Moreover, EBIs in the bone marrow of
mice with AoI have increased number of CD11b+ cells and their central macrophages, evaluated after isolation
of EBIs with gradient density sedimentation, have increased expression of P-selectin, an adhesive molecule
that attracts neutrophils.
We hypothesize that the central EBI Mφ provides a niche for both erythropoiesis and granulopoiesis at
homeostatic (baseline) hematopoiesis through intercellular interactions, while it preferentially supports
erythropoiesis in stress erythropoiesis conditions. In contrast, under conditions of inflammation, changes of the
central EBI Mφs like increased P-selectin expression, favor granulopoiesis versus erythropoiesis, leading to
AoI. Here, we propose to (1) define the spectrum of the central EBI macrophage identity in mouse and human
BM at baseline conditions, and in mouse fetal liver and spleen as models of physiological and pathological
stress erythropoiesis, (2) determine structural and functional interactions of the EBI Mφs with the granulocyte
precursors co-existing within EBIs at baseline conditions, and (3) evaluate the mechanisms by which the EBI
Mφs and granulocyte precursors in AoI suppress erythropoiesis and test if P-selectin blockage improves AoI in
animal models.
These studies will expand our knowledge on the fundamental questions regarding the identity of EBI Mφs and
their role in hematopoiesis and illuminate novel therapeutic targets and strategies to manage patients with AoI,
a common complication increasing morbidity in millions of patients with malignant, infectious, or autoimmune
diseases, worldwide.

## Key facts

- **NIH application ID:** 10130619
- **Project number:** 5R01HL152099-02
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Lionel Blanc
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $619,934
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10130619

## Citation

> US National Institutes of Health, RePORTER application 10130619, The Role of Erythroblastic Islands in Anemia of Inflammation (5R01HL152099-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10130619. Licensed CC0.

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