Figure 1.

Regulation of eosinophils by interleukin 33 (IL-33). IL-33 regulates eosinophils during three stages: development within the bone marrow, activation of mature cells, and development and/or activation of progenitors within the tissue. (A) In the bone marrow, GATA-1⁺ common myeloid progenitor (CMP) differentiates into GATA-1⁺-pre-granulocyte macrophage progenitor (Pre-GMP) (Lin⁻Sca-1⁻c-kit⁺CD41⁻CD16/32⁻CD105⁻CD150⁻GATA-1⁺), then to GATA-1⁺-granulocyte and macrophage progenitor (GMP), also known as eosinophil/mast cell progenitors (EoMP, Lin⁻Sca-1⁻c-kit⁺CD41⁺CD16/32⁺GATA-1⁺). At this early stage, IL-33 regulates the expansion of eosinophil precursor (EoPre) through differentiation of the EoMP/GMP. Since IL-33 also upregulates IL-5Rα on EoPre, it regulates commitment to the eosinophil lineage. Simultaneously, IL-33 induces another currently unidentified cell within the bone marrow to make IL-5, which promotes final eosinophil maturation. (B) In the tissue, IL-33 can activate mature eosinophils, leading to cytokine production and upregulation of CCR3, CD69, and CD11b. Notably, IL-33-driven production of GM-CSF and IL-13 promote eosinophil survival and differentiation of alternatively activated macrophages, respectively. (C) Finally, IL-33 can regulate EoP outside of the bone marrow. IL-33 increases the number of EoP in blood as well as activates EoP to produce many cytokines. Although allergens increase CCR3⁺ progenitors in tissue, it is unclear if increases in EoP in asthma patients are due to EoP leaving the bone marrow or extramedullary eosinophilopoiesis. It has yet to be determined if IL-33 also regulates eosinophilopoiesis within the tissue.