OEX_Jianxiang_2108112154

A significant complication of chronic inflammation is anemia, which may be related to disregulated activities of erythroblastic island (EBI) macrophages. GM-CSF was reported to be upregulated and attracted as a therapeutic target in many inflammatory diseases. Among EBI, we found that GM-CSF receptor is expressed preferentially and highly on EBI macrophages but not erythroblasts. GM-CSF treatment significantly decreases the human EBI formation in vitro via decreasing the adhesion molecule expression of CD163. RNA-seq analyses suggest 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 reduction in EBI numbers. To define molecular mechanism, 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 the expression of 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 have documented that GM-CSF impairs EBI formation in mouse and man. Our findings provide significant resources for anemia of inflammatory diseases and targeting GM-CSF or reprogramming EBI macrophages might be a novel strategy for these diseases.