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Open Access 01-12-2022 | Anemia | Research

GM-CSF impairs erythropoiesis by disrupting erythroblastic island formation via macrophages

Authors: Weijie Cao, Wenjuan Fan, Fang Wang, Yinyin Zhang, Guanghua Wu, Xiaojing Shi, Jian xiang Shi, Fengcai Gao, Meimei Yan, Rong Guo, Yingmei Li, Wei Li, Chunyan Du, Zhongxing Jiang

Published in: Journal of Translational Medicine | Issue 1/2022

Abstract

Anemia is a significant complication of chronic inflammation and may be related to dysregulated activities among erythroblastic island (EBI) macrophages. GM-CSF was reported to be upregulated and attracted as a therapeutic target in many inflammatory diseases. Among EBIs, we found that the GM-CSF receptor is preferentially and highly expressed among EBI macrophages but not among erythroblasts. GM-CSF treatment significantly decreases human EBI formation in vitro by decreasing the adhesion molecule expression of CD163. RNA-sequence analysis suggests that GM-CSF treatment impairs the supporting function of human EBI macrophages during erythropoiesis. GM-CSF treatment also polarizes human EBI macrophages from M2-like type to M1-like type. In addition, GM-CSF decreases mouse bone marrow (BM) erythroblasts as well as EBI macrophages, leading to a reduction in EBI numbers. In defining the molecular mechanism at work, we found that GM-CSF treatment significantly decreases the adhesion molecule expression of CD163 and Vcam1 in vivo. Importantly, GM-CSF treatment also decreases the phagocytosis rate of EBI macrophages in mouse BM as well as decreases the expression of the engulfment-related molecules Mertk, Axl, and Timd4. In addition, GM-CSF treatment polarizes mouse BM EBI macrophages from M2-like type to M1-like type. Thus, we document that GM-CSF impairs EBI formation in mice and humans. Our findings support that targeting GM-CSF or reprogramming EBI macrophages might be a novel strategy to treat anemia resulting from inflammatory diseases.

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Title: GM-CSF impairs erythropoiesis by disrupting erythroblastic island formation via macrophages
Authors: Weijie Cao
Wenjuan Fan
Fang Wang
Yinyin Zhang
Guanghua Wu
Xiaojing Shi
Jian xiang Shi
Fengcai Gao
Meimei Yan
Rong Guo
Yingmei Li
Wei Li
Chunyan Du
Zhongxing Jiang
Publication date: 01-12-2022
Publisher: BioMed Central
Keyword: Anemia
Published in: Journal of Translational Medicine / Issue 1/2022
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/s12967-021-03214-5

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