7th Annual BMRP Investigator Meeting - Abstract

Dirk Foell^1,a, Jan Ehrchen², Katarzyna Barczyk³, Johannes Roth^1,3 and Jan Däbritz¹

 

¹Departments of Pediatrics, ²Dermatology and ³Institute of Immunology, University of Münster (Münster, Germany)

 

Recent studies revealed that granulocyte–macrophage colony-stimulating factor (GM-CSF) therapy decreased disease severity in patients with active Crohn’s disease (CD). Our independent functional analysis revealed GM-CSF induced cell death in monocytes activated by TNFα or IFNg, thus promoting selective death of pro-inflammatory monocytes. We characterized the underlying mechanisms and identified GM-CSF-dependent regulation of important immune-regulatory molecules. Expression data show an up-regulation of M2-phenotype genes and down-regulation of M1-phenotype genes indicating a GM-CSF induced alternative macrophage activation. Rather than acting to suppress T cell function, GM-CSF could potentially augment a proximal, primary defect of innate immunity. GM-CSF treatment results in differentiation of a specific phenotype which may be actively involved in resolution of inflammatory reactions. We will further define the role of GM-CSF in the biology of CD by analyzing monocytic phenotypes in gut tissue from CD patients in greater detail.

  

^aPrincipal Investigator