The role of transcription factors in eosinophil differentiation

Abstract

Eosinophils play an important role in the pathogenesis of allergic diseases, such as allergic asthma. Eosinophils normally constitute only a few percent of circulating leukocytes. Increased numbers of eosinophils are found in peripheral blood, tissues, and bronchoalveolar lavage of allergic asthma patients. In the bone marrow multipotent stem cells can differentiate towards mature eosinophils, which is associated with the expression of specifi c genes, coding for e.g. the granule proteins. A highly organised network is required to coordinate these events and to maintain steady state levels of mature cells, as well as to stimulate the rapid production of specifi c cell types when needed. This thesis has focused on the transcription factors involved in the regulation of maturation of human eosinophils. An ex-vivo differentiation model was developed to study eosinophilopoiesis, and the role of transcription factors during this process was investigated. The findings were discussed with respect to hematopoietic cell fate decisions.