Monitoring eosinophils to guide therapy with Biologics in Asthma: does the compartment matter?

Abstract

Eosinophils, since their initial description by Thomas Wharton Jones in 1846, and staining characteristics by Paul Ehrlich in 1879, have been associated with asthma1 . They are produced in the bone marrow, from pluripotential stem cells, whichfirst differentiate, largely regulated by a transcription factor GATA-1, into a hybrid precursor for both basophils and eosinophils, and then into a separate eosinophil lineage. The eosinophilopoietins IL-3, GM-CSF and notably IL-5 regulatetheir further expansion and migration out of the bonemarrow into the circulation.Circulating eosinophils subsequently interactwith the endothelium by processes involving rolling, adhesion, and diapedesis. Depending on the targetorgan, eosinophils cross the endothelium into tissues by a regulated process involving the coordinatedinteraction between networks involving cytokines such as IL-13, the chemokine eotaxin-1, eosinophil adhesion molecules (α4β1, α4β7, αmβ2, αLβ2), and adhesion receptors on the endothelium (MAdCAM-1, VCAM-1, and ICAM-1). Under homeostatic conditions, eosinophils traffic into the thymus, mammary gland, uterus, and most prominently into the gastrointestinal tract.