Erythroblastic island: the niche for erythroid terminal differentiation and beyond

The erythroblastic island (EBI) is a multicellular structure defined by the presence of 1 or 2 central macrophages surrounded by at least 3 erythroblasts. EBIs were initially proposed as a specialized microenvironment exclusively for erythroid terminal differentiation. Recent advancements in techniques such as lineage tracing mouse models, imaging flow cytometry, and single-cell RNA sequencing, accumulating evidence has provided novel insights that challenge this conventional view. Notably, the erythropoietin receptor has been identified as a novel marker for EBI macrophages. Additionally, neutrophils have been identified as novel cellular components of EBIs, raising the intriguing hypothesis that EBIs may support other hematopoietic lineage cells as well. Beyond the diverse cellular components of various hematopoietic lineages, even within the erythroid lineage, an immune-prone erythroblast subpopulation has been reported, although it remains unclear whether and how these immune-prone erythroblasts mature in EBIs. These observations indicate that EBIs are a heterogeneous population. In this review, we summarize the most recent findings on EBIs, discuss their potential immune functions, and provide a perspective for future investigations.