The mechanisms of eosinophil lineage commitment

Eosinophils are involved in the pathogenesis of allergic inflammatory diseases. To establish effective therapeutic strategies for these eosinophil-related disorders including hypereosinophilic syndrome (HES), it should be important to understand the developmental pathway of eosinophils defining their lineage-committed progenitor population. We prospectively purified eosinophil lineage-committed progenitors (EoPs) downstream of granulocyte/monocyte progenitors (GMPs) by using a transgenic GATA-1 reporter mouse strain tagged with GFP. The GATA-1-activating GMP progeny were committed to the eosinophil lineage, and possessed an IL-5R α ⁺ CD34 ⁺c-kit^lo phenotype. Normal bone marrow cells also contained IL-5R α ⁺ CD34⁺ c-kit^lo EoPs that gave rise exclusively to eosinophils. EoPs significantly increased in number in response to helminth infection, suggesting that the EoP stage is physiologically involved in eosinophil production in vivo. For the eosinophil lineage-commitment, both GM-related transcription factors, PU.1 and C/EBP α, and megakaryocyte/erythrocyte-related GATA factors were required. In particular, the expression timing of C/EBP α and GATA-2 is critical for the eosinophil lineage specification.