CD163⁺ macrophages coordinate erythroblastic Island formation and iron metabolism to enable glucocorticoid-induced erythropoiesis.

Authors

Mengjia Li, Yaomei Wang, Hong Huang, Hao Sun, Mengya Gao, Mingxia Sun, Xudong Li, Zexing Liu, Donghao Liu, Meimei Yan, Zhenghua Huang, Zhen Zhang, Yuhan Hu, Bozheng Wang, Yiwei Zhou, Siyue Li, Yu An, Miao Liu, Yupeng Liu, Fengcai Gao, Fangfang Ge, Wenjuan Fan, Hao Wang, Xing Li, Fang Wang, Guomei Fu, Shiyu Zuo, Binglei Zhang, Jinxin Miao, Chong Wang, Yongping Song, Xiuli An, Weijie Cao, Linping Xu, Wei Li, Zhilei Bian

Published in

Biomarker research. Jun 27, 2026. Epub Jun 27, 2026.

Abstract

Glucocorticoids(GCs) are widely used to treat erythropoietin-resistant anemias, yet the precise mechanisms underlying their erythropoiesis-promoting effects remain incompletely understood.
This study used single-cell RNA sequencing, ATAC-seq, ChIP-seq, RNA-seq,quantitative PCR (qPCR), enzyme-linked immunosorbent assay (ELISA) and flow cytometry in vivo models (AIHA patients, CD163^-/- mice, Gypa-eGFP-cremice, Epor-tdtomato-cre mice, and Epor-eGFP-cre rats) and in vitro human erythroblastic island(EBI) formation and EBI enrichment and cytospins, Giemsa and Prussian blue staining, quantification and co-culture systems to delineate CD163⁺ macrophages coordinating erythroblastic island formation and iron metabolism.
GC promote erythropoiesis by regulating CD163-mediated EBI formation and modulating iron metabolism within EBI macrophages, a phenomenon conserved across humans, rats, and mice. We demonstrated that CD163⁺macrophages-but not their CD163^- counterparts-exhibit heightened iron metabolism in the bone marrow, and that GC-induced erythropoiesis is markedly attenuated in CD163-deficient mice due to disrupted EBI architecture and impaired iron handling. Importantly, GC therapy restores iron metabolism and mitigates inflammatory responses in BM CD163⁺macrophages, likely contributing to improved erythropoiesis in patients with autoimmune hemolytic anemia.
CD163⁺macrophages support GC-induced erythropoiesis by coordinating erythroblastic island formation and iron metabolism. These findings uncover a previously unrecognized GC-CD163-EBI axis that governs erythropoiesis and highlight the potential of targeting EBI macrophage function as a novel therapeutic strategy for anemia.

PMID:
42365354
Bibliographic data and abstract were imported from PubMed on 28 Jun 2026.

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