Mechanisms of eosinophilia in the pathogenesis of hypereosinophilic disorders

Abstract

The increased numbers of activated eosinophils in the blood and tissues that typically accompany hypereosinophilic disorders result from a variety of mechanisms. Exciting advances in translating discoveries achieved from mouse models and molecular strategies to the clinic have led to a flurry of new therapeutics specifically designed to target eosinophil-associated diseases. So far, this form of hypothesis testing in humans in vivo through pharmacology generally has supported the paradigms generated in vitro and in animal models, raising hopes that a spectrum of novel therapies soon may become available to help those who have eosinophil-associated diseases.

Figure 1. Combinatorial transcription factor “codes” that specify eosinophil lineage commitment and terminal differentiation

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 29).

Figure 2. How eosinophils are influenced to make life or death decisions

Stimuli that are known to promote eosinophil priming and survival are displayed, and are contrasted with those that facilitate eosinophil apoptosis. Also shown are some of the phenotypic characteristics that accompany the primed state compared to those seen in cells undergoing apoptosis. Art by Jacqueline Schaffer.