Monocytes Generated by Interleukin-6-treated Human Hematopoietic Stem and Progenitor Cells Secrete Calprotectin That Inhibits Erythropoiesis

Overview

Journal iScience

Publisher Cell Press

Date 2025 Jan 15

PMID 39811665

Authors

Valentine Marchand

Lucie Laplane

Louis Valensi

Isabelle Plo

Marine Aglave

Aymeric Silvin

Florence Pasquier

Francoise Porteu

William Vainchenker

Dorothee Selimoglu-Buet

Nathalie Droin

Hana Raslova

Virginie Marcel

Jean-Jacques Diaz

Michaela Fontenay

Eric Solary

Affiliations

Soon will be listed here.

Abstract

Elevated circulating levels of calprotectin (CAL), the S100A8/A9 heterodimer, are biomarkers of severe systemic inflammation. Here, we investigate the effects of CAL on early human hematopoiesis. CAL demonstrates limited impact on gene expression in stem and progenitor cells, in contrast with interleukin-6 (IL6), which promotes the expression of the and genes in hematopoietic progenitors and the generation of monocytes that release CAL. The main target of CAL is an erythroid-megakaryocyte progenitor (EMP) subset. CAL prevents both erythropoietin-driven differentiation of healthy progenitors and JAK2-V617F-driven erythropoiesis. In the context of JAK2-V617F, CAL also promotes the expression of and genes in monocytes. The signature of CAL effects is detected in the bone marrow progenitors of patients with myeloid malignancy or severe infection. These results position CAL as a mediator of IL6 effects on triggering anemia during inflammation, an effect that is amplified in the context of JAK2-V617F-driven hematopoiesis.

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