PMC

HSC, CD34+ hematopoietic stem cells; CMP, common myeloid progenitors; GMP granulocyte-macrophage progenitors; MEP, megakaryocyte/erythroid progenitors. GATA-1 is both necessary and sufficient to drive eosinophil development, and C/EBPε is required for eosinophil terminal differentiation. It remains unclear whether human eosinophils can also develop directly from CMP (Modified and updated from reference ).

Eosinophils develop in the bone marrow. Transcription factor (such as Δdbl-GATA-1) and cytokines (such as IL-5, IL-3 and GM-CSF) are essential for their differentiation from an hematopoietic stem cell into the mature eosinophil. Once mature, IL-5 controls the eosinophil migration from the bone marrow to the blood. At baseline, eosinophils localize in the thymus, GI tract, uterus and mammary gland. Eosinophils are able to express and to secrete, at baseline or upon stimulation, a large variety of mediators (cytokines, granule proteins, lipid mediators). Eosinophils are putative antigen presenting cells and play a role in mast cell activation, T cell communication and function.

Proposed mechanisms of hypereosinophilia-related changes. With the appropriate trigger, cytokines or ligands (IL-3, IL-5, GM-CSF, tumor necrosis factor-alpha, interferon-gamma, leptin, CD40) can promote eosinophil proliferation and survival. Different cytokines or ligands (such as Fas, TGF beta, SIGLEC-8, CD30, and corticosteroids) can also facilitate eosinophil apoptosis. * Protein mediators include MBP, ECP, EPX, and eosinophil derived NGF. Abbreviations: CCR, chemokine receptor; CD, cluster of differentiation; ECP, eosinophil cationic protein; GM-CSF, granulocyte-macrophage colony-stimulating factor; HE, hypereosinophilia; HES, hypereosinophilic syndrome; EPX, eosinophil peroxidase; IG, immunoglobulin; IL, interleukin; L-HES, lymphocytic variant of hypereosinophilia; MBP, major basic protein; M-HES, myeloproliferative hypereosinophilia; NGF, nerve growth factor; SIGLEC-8: sialic acid-binding immunoglobulin-like lectin 8; TGF, transforming growth factor; TLR, toll-like receptor. Adapted from reference [].

Transcription factors that instruct eosinophil differentiation. A number of transcription factors control eosinophil-lineage commitment and differentiation to mature eosinophils. A decline in FOG-1 and increased IRF8 up-regulates C/EBPα, with subsequent GATA-1/GATA-2 expression. Collective IRF8, PU.1, C/EBPα, and C/EBPε expression results in eosinophil-lineage commitment, followed by collaboration between C/EBPε, PU.1, GATA-1, and GATA-2 for progression to mature eosinophils. XBP1 and balanced ID1/ID2 expression allows for eosinophil granule protein synthesis and survival. Abbreviations: C/EBPα= CAAT/enhancer binding protein alpha; C/EBP = CAAT/enhancer binding protein epsilon; EoP = Eosinophil progenitor; FOG-1 = Friend of GATA-1; GATA-1 = Globin transcription binding factor-1; HPC = Hematopoietic progenitor cells; ID1 = Inhibitor of DNA-binding proteins 1; ID2 = Inhibitor of DNA-binding proteins 2; IL-5Rα = Interleukin-5 receptor alpha; IRF8 = Interferon regulatory factor 8.